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

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    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.

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

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    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...

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

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

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    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.

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

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    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...

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

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    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.

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

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    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.

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

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    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.

  9. 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.

  10. 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.

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

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    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.

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

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    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.

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

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    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.

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

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

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    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.

  16. 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)

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

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    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.

  18. 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.

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    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

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

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    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.

  20. 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.)

  1. 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.

  2. 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.

  3. 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

  4. 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.

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

    Science.gov (United States)

    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.

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

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    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.

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

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    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

  9. 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.

  10. 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....

  11. 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.

  12. 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.

  13. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. L-Arginine Supplementation and Metabolism in Asthma

    Directory of Open Access Journals (Sweden)

    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.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. [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.

  5. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  8. 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

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. 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.

  15. 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

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

    Science.gov (United States)

    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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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....

  19. 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 ...

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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 ...

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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...

  1. 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 ...

  2. 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

  3. 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.

  4. 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.

  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

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

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    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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

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

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    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.

  14. 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....

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. [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.

  3. 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

  4. 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

  5. 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.

  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. 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.

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

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    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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

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

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    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. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. 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.

  3. 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.

  4. 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)

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. Play Therapy: Role in Reading Improvement.

    Science.gov (United States)

    Carmichael, Karla

    1991-01-01

    Reviews the literature concerning the role of play therapy (particularly sandplay and nondirected play therapy) in the improvement of reading. Suggests that the role of play therapy is to support the child, encourage the child, and build self-esteem thus creating the optimal learning environment for reading improvement. (RS)

  14. 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.

  15. 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.

  16. 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)

  17. 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.

  18. 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)

  19. 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.

  20. Effect of in ovo injection with L-arginine on productive and ...

    African Journals Online (AJOL)

    p2492989

    Significant decreases were recorded in blood serum cholesterol, total lipids ... 2% and 3% arginine, resulted in a significant improvement in the productive ... Various factors play important roles in birds in influencing hatchability efficiency and growth ... in the yolk sac may not be sufficient to supply in the maintenance energy.

  1. [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.

  2. 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.

  3. 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

  4. 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 ...

  5. 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

  6. [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.

  7. 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)

  8. 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.

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

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    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.

  10. 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.

  11. 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

  12. 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, ...

  13. Improving adherence to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Nischal K

    2005-01-01

    Full Text Available Antiretroviral therapy (ART has transformed HIV infection into a treatable, chronic condition. However, the need to continue treatment for decades rather than years, calls for a long-term perspective of ART. Adherence to the regimen is essential for successful treatment and sustained viral control. Studies have indicated that at least 95% adherence to ART regimens is optimal. It has been demonstrated that a 10% higher level of adherence results in a 21% reduction in disease progression. The various factors affecting success of ART are social aspects like motivation to begin therapy, ability to adhere to therapy, lifestyle pattern, financial support, family support, pros and cons of starting therapy and pharmacological aspects like tolerability of the regimen, availability of the drugs. Also, the regimen′s pill burden, dosing frequency, food requirements, convenience, toxicity and drug interaction profile compared with other regimens are to be considered before starting ART. The lack of trust between clinician and patient, active drug and alcohol use, active mental illness (e.g. depression, lack of patient education and inability of patients to identify their medications, lack of reliable access to primary medical care or medication are considered to be predictors of inadequate adherence. Interventions at various levels, viz. patient level, medication level, healthcare level and community level, boost adherence and overall outcome of ART.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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).

  2. 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...

  3. Improved exercise myocardial perfusion during lidoflazine therapy

    International Nuclear Information System (INIS)

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-01-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise

  4. 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

  5. Toyota production system quality improvement initiative improves perioperative antibiotic therapy.

    Science.gov (United States)

    Burkitt, Kelly H; Mor, Maria K; Jain, Rajiv; Kruszewski, Matthew S; McCray, Ellesha E; Moreland, Michael E; Muder, Robert R; Obrosky, David Scott; Sevick, Mary Ann; Wilson, Mark A; Fine, Michael J

    2009-09-01

    To assess the role of a Toyota production system (TPS) quality improvement (QI) intervention on appropriateness of perioperative antibiotic therapy and in length of hospital stay (LOS) among surgical patients. Pre-post quasi-experimental study using local and national retrospective cohorts. We used TPS methods to implement a multifaceted intervention to reduce nosocomial methicillin-resistant Staphylococcus aureus infections on a Veterans Affairs surgical unit, which led to a QI intervention targeting appropriate perioperative antibiotic prophylaxis. Appropriate perioperative antibiotic therapy was defined as selection of the recommended antibiotic agents for a duration not exceeding 24 hours from the time of the operation. The local computerized medical record system was used to identify patients undergoing the 25 most common surgical procedures and to examine changes in appropriate antibiotic therapy and LOS over time. Overall, 2550 surgical admissions were identified from the local computerized medical records. The proportion of surgical admissions receiving appropriate perioperative antibiotics was significantly higher (P <.01) in 2004 after initiation of the TPS intervention (44.0%) compared with the previous 4 years (range, 23.4%-29.8%) primarily because of improvements in compliance with antibiotic therapy duration rather than appropriate antibiotic selection. There was no statistically significant decrease in LOS over time. The use of TPS methods resulted in a QI intervention that was associated with an increase in appropriate perioperative antibiotic therapy among surgical patients, without affecting LOS.

  6. 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...

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Therapy with granulocyte colony-stimulating factor in the chronic stage, but not in the acute stage, improves experimental autoimmune myocarditis in rats via nitric oxide.

    Science.gov (United States)

    Shimada, Kana; Okabe, Taka-aki; Mikami, Yu; Hattori, Miki; Fujita, Masatoshi; Kishimoto, Chiharu

    2010-09-01

    We systematically investigated serial efficacy of granulocyte colony-stimulating factor (G-CSF) therapy upon experimental autoimmune myocarditis (EAM) in rats treated with and without the inhibition of nitric oxide (NO) with the analyses of tissue regeneration. G-CSF could mobilize multipotent progenitor cells of bone marrow into the peripheral blood and may improve ventricular function. A rat model of porcine myosin-induced EAM was used. After the immunization of myosin, G-CSF (10 microg/kg/day) or saline was injected intraperitoneally on days 0-21 in experiment 1 and on days 21-42 in experiment 2. Additional myosin-immunized rats were orally given 25 mg/kg/day of N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase (NOS), in each experiment (each group; n=8-21). Serum cytokines and peripheral blood cell counts were measured in each group. In experiment 1, G-CSF treatment aggravated cardiac pathology associated with increased macrophage inflammatory protein-2 (MIP-2) and interleukin-6 (IL-6) levels and enhanced superoxide production. In experiment 2, G-CSF treatment reduced the severity of myocarditis with increased capillary density and improved left ventricular ejection fraction. In the rats with EAM treated with G-CSF associated with oral L-NAME treatment in experiment 2, the severity of myocarditis was not reduced. Myocardial c-kit(+) cells were demonstrated only in G-CSF-treated group in experiment 2 but not in other groups. G-CSF has differential effects on EAM in rats associated with the modulation of cytokine network. The overwhelming superoxide production by G-CSF administration in the acute stage may worsen the disease. G-CSF therapy improved cardiac function via NO system in a rat model of myocarditis in the chronic stage, but not in the acute stage, possibly through the myocardial regeneration and acceleration of healing process. Copyright 2010 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. 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.

  3. 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.)

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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)

  11. Improvement of cycloid psychosis following electroconvulsive therapy.

    Science.gov (United States)

    Holm, Jonas; Brus, Ole; Båve, Ullvi; Landen, Mikael; Lundberg, Johan; Nordanskog, Pia; von Knorring, Lars; Nordenskjöld, Axel

    2017-08-01

    The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness. The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome. Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n = 42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011-2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fisher's exact test. The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (p < 0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p = 0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1, p = 0.31). None of the other investigated potential predictors was statistically significantly associated with outcome. ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies. The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis.

  12. 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.

  13. 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

  14. 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.

  15. 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

  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. Improving compliance with hormonal replacement therapy in primary osteoporosis prevention

    DEFF Research Database (Denmark)

    Vestergaard, P; Hermann, A P; Gram, J

    1997-01-01

    To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule.......To evaluate whether introduction of treatment alternatives would improve compliance with hormonal replacement therapy (HRT) as primary osteoporosis prevention in women not tolerating the first line osteoporosis prevention schedule....

  20. Does Music Therapy Improve Anxiety and Depression in Alzheimer's Patients?

    Science.gov (United States)

    de la Rubia Ortí, José Enrique; García-Pardo, María Pilar; Iranzo, Carmen Cabañés; Madrigal, José Joaquin Cerón; Castillo, Sandra Sancho; Rochina, Mariano Julián; Gascó, Vicente Javier Prado

    2018-01-01

    To evaluate the effectiveness of the implementation of a short protocol of music therapy as a tool to reduce stress and improve the emotional state in patients with mild Alzheimer's disease. A sample of 25 patients with mild Alzheimer's received therapy based on the application of a music therapy session lasting 60 min. Before and after the therapy, patient saliva was collected to quantify the level of salivary cortisol using the Enzyme-Linked ImmunoSorbent Assay (ELISA) immunoassay technique and a questionnaire was completed to measure anxiety and depression (Hospital Anxiety and Depression Scale). The results show that the application of this therapy lowers the level of stress and decreases significantly depression and anxiety, establishing a linear correlation between the variation of these variables and the variation of cortisol. A short protocol of music therapy can be an alternative medicine to improve emotional variables in Alzheimer patients.

  1. 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.

  2. Metabolomics has the potential to improve drug therapy

    DEFF Research Database (Denmark)

    Stage, Claus; Jürgens, Gesche; Dalhoff, Kim Peder

    2014-01-01

    Until now drug therapy has primarily been controlled by dose titration on the basis of effects and side effects. However, a lot of people being treated with a drug experience too little effect or too many side effects. Therefore it will be advantageous to improve drug therapy and make it even more...

  3. Improve T Cell Therapy in Neuroblastoma

    Science.gov (United States)

    2012-07-01

    Savoldo B, Vigouroux S et al. T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte...Natl Acad Sci U S A. 2004;101(suppl 2):14622–14626. 8. Eghtesad S, Morel PA, Clemens PR. The companions : regulatory T cells and gene therapy...were euthanized and examined for NKT cell localiza- tion to the tumor tissues. Animals treated with anti-CCL2 or anti- CCL20 mAb had lower frequency

  4. Stem Cell Therapy to Improve Burn Wound Healing

    Science.gov (United States)

    2017-03-01

    Award Number: W81XWH-13-2-0024 TITLE: Stem Cell Therapy to Improve Burn Wound Healing PRINCIPAL INVESTIGATOR: Carl Schulman, MD, PhD, MSPH...NUMBER Stem Cell Therapy to Improve Burn Wound Healing 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Carl Schulman, MD, PhD, MSPH...treatments, steroid injections, and compression garments. Mesenchymal stem cells (MSC’s) have been used in a variety of clinical applications to repair

  5. 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

  6. 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)

  7. Kinetic therapy improves oxygenation in critically ill pediatric patients.

    Science.gov (United States)

    Schultz, Theresa Ryan; Lin, Richard; Francis, Barbara A; Hales, Roberta L; Colborn, Shawn; Napoli, Linda A; Helfaer, Mark A

    2005-07-01

    To compare changes in oxygenation after manual turning and percussion (standard therapy) and after automated rotation and percussion (kinetic therapy). Randomized crossover trial. General and cardiac pediatric intensive care units. Intubated and mechanically ventilated pediatric patients who had an arterial catheter and no contraindications to using a PediDyne bed. Patients were placed on a PediDyne bed (Kinetic Concepts) and received 18 hrs blocks of standard and kinetic therapy in an order determined by randomization. Arterial blood gases were measured every 2 hrs during each phase of therapy. Oxygenation index and arterial-alveolar oxygen tension difference [P(A-a)O(2)] were calculated. Indexes calculated at baseline and after each 18-hr phase of therapy were analyzed. Fifty patients were enrolled. Data from 15 patients were either not collected or not used due to reasons that included violation of protocol and inability to tolerate the therapies in the study. Indexes of oxygenation were not normally distributed and were compared using Wilcoxon signed rank testing. Both therapies led to improvements in oxygenation, but only those from kinetic therapy achieved statistical significance. In patients receiving kinetic therapy first, median oxygenation index decreased from 7.4 to 6.19 (p = .015). The median P(A-a)O(2) decreased from 165.2 to 126.4 (p = .023). There were continued improvements in oxygenation after the subsequent period of standard therapy, with the median oxygenation index decreasing to 5.52 and median P(A-a)O(2) decreasing to 116.0, but these changes were not significant (p = .365 and .121, respectively). When standard therapy was first, the median oxygenation index decreased from 8.83 to 8.71 and the median P(a-a)o(2) decreased from 195.4 to 186.6. Neither change was significant. Median oxygenation index after the subsequent period of kinetic therapy was significantly lower (7.91, p = .044) and median P(A-a)O(2) trended lower (143.4, p = .077

  8. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Franklin King

    2015-12-01

    Full Text Available Introduction: Delayed posthypoxic leukoencephalopathy (DPHL may result from a variety of hypoxic insults, including respiratory depression from an opiate overdose. The underlying pathophysiological mechanism of DPHL remains uncertain. We describe a patient with a typical case of DPHL who responded clinically to antioxidant treatment. Methods: Clinical, serological, and radiographic investigations were undertaken in the evaluation of the patient. Results: A 63-year-old man developed altered mental status 10 days following recovery from an opiate overdose and aspiration pneumonia that required intubation. The clinical course and brain imaging were consistent with DPHL. Initiation of antioxidant therapy with vitamin E, vitamin C, B-complex vitamins, and coenzyme Q10 coincided with the prompt reversal of clinical deterioration. Conclusions: The potential therapeutic effect of antioxidants on DPHL needs to be explored in future cases. If this relationship indeed holds true, it would be consistent with the hypothesis that formation of reactive oxygen species during reperfusion plays a role in the pathophysiology of this disorder.

  9. Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus

    NARCIS (Netherlands)

    Subiabre, Mario; Silva, Luis; Villalobos-Labra, Roberto; Toledo, Fernando; Paublo, Mario; López, Marcia A.; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase

  10. Improving Islet Engraftment by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Xiaojie Wang

    2011-01-01

    Full Text Available Islet cell transplantation is currently the only feasible long-term treatment option for patients with type 1 diabetes. However, the majority of transplanted islets experience damage and apoptosis during the isolation process, a blood-mediated inflammatory microenvironment in the portal vein upon islet infusion, hypoxia induced by the low oxygenated milieu, and poor-revascularization-mediated lack of nutrients, and impaired hormone modulation in the local transplanted site. Strategies using genetic modification methods through overexpression or silencing of those proteins involved in promoting new formation of blood vessels or inhibition of apoptosis may overcome these hurdles and improve islet engraftment outcomes.

  11. Animal-Assisted Therapy for Improving Human Health

    Directory of Open Access Journals (Sweden)

    Sibel Cevizci

    2009-06-01

    Full Text Available ABSTRACT Animal Assisted Therapy (AAT or Pet Therapy is an adjunctive therapy by taking advantage of human and animal interaction, activate the physiological and psychological mechanisms, initiate positive changes improving health in metabolism. In recent years, this interaction are in use to treat psychological and psychiatric disorders such as stress, depression, loneliness, pervasive developmental disorders affect negatively to human health. Furthermore, AAT has been increasingly used to improve quality of life, hypertension, cardiovascular diseases, chronic illnesses such as cancer and AIDS. The aim of this paper is to identify AAT by reviewing human and animal interaction, evaluate how AAT has a scientific background from past to now. Also, we aim to give some information about the risks, institutional applications, some factors referring AAT’s mechanism of action and chronic diseases, psychological and physical improvements provided with animal assisted therapies. The therapy results will be evaluated more advisable providing AAT is being applied with public health specialist, veterinarian, physician, psychologist, psychiatrist and veterinary public health experts who are monitor applications. Especially, the psychosomatic effects result from physical, emotional and play mechanism of action of HDT can be used for improving quality of life in individuals with chronic diseases. In Turkey, there is no any investigation which have been performed in this scientific field. It is quitely important to evaluate the benefits of this therapy accurately and to select various methods proper to diseases. Consequently, it is obvious that AAT will be considered by the healthcare services as a supportive therapy process for improving human health in Turkey and needs further studies. [TAF Prev Med Bull 2009; 8(3.000: 263-272

  12. Improving access to psychological therapies in voice disorders: a cognitive behavioural therapy model.

    Science.gov (United States)

    Miller, Tracy; Deary, Vincent; Patterson, Jo

    2014-06-01

    The improving access to psychological therapies initiative has highlighted the importance of managing mental health problems effectively, and research has shown excellent outcomes from cognitive behavioural therapy (CBT) interventions. Patients presenting with functional dysphonia will often also describe psychological distress including anxiety, depression and reduced general well-being, and it is felt that effective voice therapy needs to include the management of psychological well-being. The evidence for the use of CBT enhanced voice therapy is limited to date. Recent research has only started to identify the benefits of this approach and questions regarding how to achieve and maintain competence are essential. Voice therapy outcomes are positive and patients receiving CBT with voice therapy have shown more improvement in their general well-being and distress. CBT is a very well evidenced therapy and recommended by The National Institute for Health and Care Excellence (NICE) as the treatment of choice for mental health difficulties and medically unexplained symptoms. Allied health professionals are increasingly being trained to use CBT skills in the management of a number of symptoms/illnesses, and this should be considered for the management of functional dysphonia. However, there is a need for more research and detailed consideration of how therapists should be trained and supervised and how cost-effective this approach may be.

  13. Arginine Adjunctive Therapy in Active Tuberculosis

    Directory of Open Access Journals (Sweden)

    Aliasghar Farazi

    2015-01-01

    Full Text Available Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18. Results. Arginine supplementation reduced constitutional symptoms (P=0.032 in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P=0.032 and P=0.04 and a reduced CRP at the end of the first month of treatment (P=0.03 versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2.

  14. Pulmonary functions of children with asthma improve following massage therapy.

    Science.gov (United States)

    Fattah, Mohammed Abdel; Hamdy, Basant

    2011-11-01

    This study aimed at evaluating the effect of massage therapy on the pulmonary functions of stable Egyptian children with asthma. This study was an open, randomized, controlled trial. The study was conducted in pediatric allergy and chest unit of the New Children's Hospital of Cairo University, Egypt. Sixty (60) children with asthma were divided randomly into two equal groups: massage therapy group and control group. Subjects in the massage therapy group received a 20-minute massage therapy by their parents at home before bedtime every night for 5 weeks in addition to the standard asthma treatment. The control group received the standard asthma treatment alone for 5 weeks. Spirometry was performed for all children on the first and last days of the study. Forced expiratory flow in first second (FEV1), forced vital capacity (FVC), FEV1/FVC and peak expiratory flow (PEF) were recorded. At the end of the study, mean FEV1 of the massage therapy group was significantly higher than controls (2.3-0.8 L versus 1.9-0.9 L, p=0.04). There was no significant difference in FVC (2.5-0.8 L versus 2.7-0.7 L, p=0.43). However, FEV1/FVC ratio showed a significant improvement in the massage therapy group (92.3-21.5 versus 69.5-17, pmassage therapy in pediatric asthma is suggested. It improved the key pulmonary functions of the children, namely, FEV1 and FEV1/FVC ratio. However, further research on a larger scale is warranted. © Mary Ann Liebert, Inc.

  15. 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

  16. The Effectiveness of Gestalt Therapy and Cognitive Therapy on Improvement of Life Quality of War Veterans

    Directory of Open Access Journals (Sweden)

    S Sadeghi

    2012-02-01

    Full Text Available Background & Aim: The imposed war burdened a lot of problems on the society of Iran during the past few years. In this course, veterans didn’t immune from its harmful effects. The aim of the present study was to determine the effectiveness of integrated group gestalt therapy and cognitive therapy on improvement of quality of life of veterans of city of Jahrom, Iran. Methods: The present clinical trial study was conducted on thirty veterans of Jahrom in 2010. The subjects included all the war veterans of Jahrom, 820 with 25-69 percent physical damage. Random sampling was executed and the world Health Organization life quality questionnaire (WHOQOL-BREF was given to 150 of them. Fifteen people in each group were replaced by another fifteen people. The test group received eight sessions of group consultation in Gestalt therapy and cognition therapy ways, but the control group received no therapy. The gathered data was analyzed using ANOVA test. Results: The result of this study showed that-there is a significant difference between the life quality dimensions (physical health, mental health, life environment and social relations between the test and control group (p=0.001. Conclusion: The results of this study showed that the integrated of group counseling by gestalt therapy and cognitive therapy had an influence on increasing the veteran’s life qualifications in aspects of physical health, mental health, life environment and social relations.

  17. IMPROVING FUNCTIONAL INDEPENDENCE OF PATIENTS WITH MULTIPLE SCLEROSIS BY PHYSICAL THERAPY AND OCCUPATIONAL THERAPY

    Directory of Open Access Journals (Sweden)

    Ana-Maria Ticărat

    2011-06-01

    Full Text Available Introduction. Patients with multiple sclerosis can have a normal life despite of their real or possible disability and of the progressive nature of it. Scope. Patients who follow physical therapy and occupational therapy will have an increased quality of life and a greater functional independence.Methods. The randomized study was made on 7 patients with multiple sclerosis, from Oradea Day Centre, 3 times/week, ages between 35 – 55 years, functional level between mild and sever. Assessment and rehabilitation methods: inspection, BARTHEL Index. Frenkel method, brething exercises, weights exercises, gait exercises, writind exercises and games were used in the rehabilitation process. Group therapies: sociotherapy, arttherapy, music therapy. Results analysis consisted of the comparison of baseline and final means.Results. By analizing baseline and final means for Barthel Index for each functon separately, it was shown a mild improvement of functional independence for almost assessed functions, with at least 1-1,5 points.Conclusions. Persons with multiple sclerosis who follow physical therapy and occupational therapy presents a better functional independence after the treatment.

  18. Sleep Quality Improvement During Cognitive Behavioral Therapy for Anxiety Disorders.

    Science.gov (United States)

    Ramsawh, Holly J; Bomyea, Jessica; Stein, Murray B; Cissell, Shadha H; Lang, Ariel J

    2016-01-01

    Despite the ubiquity of sleep complaints among individuals with anxiety disorders, few prior studies have examined whether sleep quality improves during anxiety treatment. The current study examined pre- to posttreatment sleep quality improvement during cognitive behavioral therapy (CBT) for panic disorder (PD; n = 26) or generalized anxiety disorder (GAD; n = 24). Among sleep quality indices, only global sleep quality and sleep latency improved significantly (but modestly) during CBT. Sleep quality improvement was greater for treatment responders, but did not vary by diagnosis. Additionally, poor baseline sleep quality was independently associated with worse anxiety treatment outcome, as measured by higher intolerance of uncertainty. Additional intervention targeting sleep prior to or during CBT for anxiety may be beneficial for poor sleepers.

  19. Adjuvant Medications That Improve Survival after Locoregional Therapy.

    Science.gov (United States)

    Boas, F Edward; Ziv, Etay; Yarmohammadi, Hooman; Brown, Karen T; Erinjeri, Joseph P; Sofocleous, Constantinos T; Harding, James J; Solomon, Stephen B

    2017-07-01

    To determine if outpatient medications taken at the time of liver tumor embolization or ablation affect survival. A retrospective review was done of 2,032 liver tumor embolization, radioembolization, and ablation procedures performed in 1,092 patients from June 2009 to April 2016. Pathology, hepatocellular carcinoma (HCC) stage (American Joint Committee on Cancer), neuroendocrine tumor (NET) grade, initial locoregional therapy, overall survival after initial locoregional therapy, Child-Pugh score, Eastern Cooperative Oncology Group performance status, Charlson Comorbidity Index, and outpatient medications taken at the time of locoregional therapy were analyzed for each patient. Kaplan-Meier survival curves were calculated for patients taking 29 medications or medication classes (including prescription and nonprescription medications) for reasons unrelated to their primary cancer diagnosis. Kaplan-Meier curves were compared using the log-rank test. For patients with HCC initially treated with embolization (n = 304 patients), the following medications were associated with improved survival when taken at the time of embolization: beta-blockers (P = .0007), aspirin (P = .0008) and other nonsteroidal antiinflammatory drugs (P = .009), proton pump inhibitors (P = .004), and antivirals for hepatitis B or C (P = .01). For colorectal liver metastases initially treated with ablation (n = 172 patients), beta-blockers were associated with improved survival when taken at the time of ablation (P = .02). Aspirin and beta-blockers are associated with significantly improved survival when taken at the time of embolization for HCC. Aspirin was not associated with survival differences after locoregional therapy for NET or colorectal liver metastases, suggesting an HCC-specific effect. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  20. Gene transfer strategies for improving radiolabeled peptide imaging and therapy

    International Nuclear Information System (INIS)

    Rogers, B.E.; Buchsbaum, D.J.; Zinn, K.R.

    2000-01-01

    Utilization of molecular biology techniques offers attractive options in nuclear medicine for improving cancer imaging and therapy with radiolabeled peptides. Two of these options include utilization of phage-panning to identify novel tumor specific peptides or single chain antibodies and gene transfer techniques to increase the antibodies and gene transfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. The group has focused on the latter approach for improving radiolabeled peptide imaging and therapy. The most widely used gene transfer vectors in clinical gene therapy trials include retrovirus, cationic lipids and adenovirus. It has been utilized adenovirus vectors for gene transfer because of their ability to accomplish efficient in vivo gene transfer. Adenovirus vectors encoding the genes for a variety of antigens/receptors (carcinoembryonic antigen, gastrin-releasing peptide receptor, somatostatin receptor subtype 2 (SSTr2) have all shown that their expression is increased on cancer cells both in vitro and in vivo following adenovirus infection. Of particular interest has been the adenovirus encoding for SSTr2 (AdCMVSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in animal models. The use of these analogues in combination with AdCMVSSTr2 is a promising approach for improving the detection sensitivity and therapeutic efficacy of these radiolabeled peptides against solid tumors. In addition, it has been proposed the use of SSTr2 as a marker for imaging the expression of another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allow for non-invasive monitoring of gene delivery to tumor sites

  1. Improved outcome in solitary bone plasmacytomata with combined therapy.

    Science.gov (United States)

    Avilés, A; Huerta-Guzmán, J; Delgado, S; Fernández, A; Díaz-Maqueo, J C

    1996-09-01

    Solitary bone plasmacytoma (SBP) is a rare presentation of plasma cell dyscrasias. Radiotherapy has been considered the treatment of choice, however, most patients will develop multiple myeloma, 3 to 10 years after initial diagnosis and treatment. No innovations have been introduced in the treatment of SBP in the last 30 years. We began a prospective clinical trial to assess the efficacy and toxicity of adjuvant chemotherapy with low doses of melphalan and prednisone administered to patients with SBP after radiation therapy in an attempt to improve the disease-free survival and overall survival. Between 1982 and 1989, 53 patients with SBP were randomly assigned to be treated with either local radiotherapy with doses ranged from 4000 to 5000 cGy to achieve local control of disease (28 patients) or the same radiotherapy schedule followed by melphalan and prednisone given every 6 weeks for 3 years (25 patients). After a median follow-up of 8.9 years, disease-free survival and overall survival were improved in patients who were treated with combined therapy, 22 patients remain alive and free of disease in the combined treatment group compared to only 13 patients in the radiotherapy group (p radiotherapy in patients with SBP improved duration of remission and survival without severe side-effects. However, as with other studies in SBP, the group was too small to draw definitive conclusions and more controlled clinical trials are necessary to define the role of this therapeutic approach in patients with SBP.

  2. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  3. 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.

  4. Effects of in ovo feeding of l-arginine on hatchability, hatching time, early posthatch development, and carcass traits in domestic pigeons (Columba livia).

    Science.gov (United States)

    Zhang, X Y; Wan, X P; Miao, L P; Zou, X T; Dong, X Y

    2017-10-01

    The objective of this research was to test the hypothesis that in ovo feeding of arginine (Arg) may improve hatchability and posthatch performance in domestic pigeons (). A completely randomized design ( = 3) with an Arg feeding treatment (Arg group, 1.14 mg Arg dissolved in 200 μL of 0.75% NaCl buffered saline as 1% concentration compared to total Arg in the egg), a buffered saline feeding treatment (SC group, 7.5 g NaCl dissolved in 1 L sterile distilled water as the concentration of poultry physiological saline), and a nonfeeding treatment (NC group) was used. Six squabs from each treatment were randomly sampled on day of hatch (DOH), posthatch d 7 (D7), and posthatch d 14 (D14), respectively. Hatchability, hatch time, BW, organ development, and carcass traits were examined. Results showed that in ovo feeding of the Arg solution increased ( < 0.05) the hatchability and advanced ( < 0.05) the hatching time in comparison with those of the other groups. Body weight of pigeon squabs that received Arg in ovo feeding was heavier ( < 0.05) on DOH and D14 than that of the NC group, and a greater ( < 0.05) BW gain from DOH to D14 and D7 to D14 was observed. Three clusters of 12 organs were classified according to the changes of organ indices. Squabs provided the Arg in ovo feeding treatment gained a priority in organ development. The heart index and gizzard index on D7 and the proventriculus index on D14 of squabs receiving Arg in ovo feeding were increased ( < 0.05) compared to those of the other groups. The brain index on DOH, the small intestine index and pancreas index on D7, and the liver index, pancreas index, and spleen index on D14 of squabs fed Arg were higher ( < 0.05) than those of the NC group. The spleen index on D7 and the small intestine index on D14 of squabs provided the Arg feeding treatment were enhanced ( < 0.05) compared with those of the SC group. The semieviscerated carcass weight of squabs receiving Arg was higher ( < 0.05) on D14 than that of

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    Science.gov (United States)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  10. Clinical audit training improves undergraduates' performance in root canal therapy.

    Science.gov (United States)

    Fong, J Y M; Tan, V J H; Lee, J R; Tong, Z G M; Foong, Y K; Tan, J M E; Parolia, A; Pau, A

    2017-12-20

    To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  12. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.

    Science.gov (United States)

    Al-Zaidy, Samiah A; Sahenk, Zarife; Rodino-Klapac, Louise R; Kaspar, Brian; Mendell, Jerry R

    2015-09-02

    Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.

  13. Improved animal models for testing gene therapy for atherosclerosis.

    Science.gov (United States)

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  14. Narrative therapy for adults with major depressive disorder: improved symptom and interpersonal outcomes.

    Science.gov (United States)

    Vromans, Lynette P; Schweitzer, Robert D

    2011-01-01

    This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder.

  15. Metformin use and improved response to therapy in rectal cancer

    International Nuclear Information System (INIS)

    Skinner, Heath D.; Crane, Christopher H.; Garrett, Christopher R.; Eng, Cathy; Chang, George J.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Kelly, Patrick; Sandulache, Vlad C.; Delclos, Marc E.; Krishnan, Sunil; Das, Prajnan

    2013-01-01

    Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8–63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study

  16. Considerations to improve the safety of cervical spine manual therapy.

    Science.gov (United States)

    Hutting, Nathan; Kerry, Roger; Coppieters, Michel W; Scholten-Peeters, Gwendolijne G M

    2018-02-01

    Manipulation and mobilisation of the cervical spine are well established interventions in the management of patients with headache and/or neck pain. However, their benefits are accompanied by potential, yet rare risks in terms of serious adverse events, including neurovascular insult to the brain. A recent international framework for risk assessment and management offers directions in the mitigation of this risk by facilitating sound clinical reasoning. The aim of this article is to critically reflect on and summarize the current knowledge about cervical spine manual therapy and to provide guidance for clinical reasoning for cervical spine manual therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 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

    from C than in OB rats [EC50 (x10-7M: C = 1.84 (0.83-4.07, O = 2.49 (1.41-4.38; L-NAME presence C = 0.02 (0.01-0.04*, O = 0.21 (0.11-0.40*†,*p < 0.05 vs respective control, †p < 0.05 vs control plus L-NAME, n = 6-7]. None of the protocols altered the reactivity to noradrenaline of denuded aortas. CONCLUSION: High-fat diet-induced obesity promotes metabolic and vascular alterations. The vascular alteration involved an endothelial L-arginine/NO pathway improvement was probably correlated to diet-induced hyperinsulinemia and hyperleptinemia. The greater resistance to L-NAME effects in aorta of obese rats raises concerns about the lower cardiovascular vulnerability of obese individuals in the presence of associated pathologies that impair NO-system activity.

  18. Can low-intensity extracorporeal shockwave therapy improve erectile dysfunction?

    DEFF Research Database (Denmark)

    Olsen, Anne B; Persiani, Marie; Boie, Sidsel

    2015-01-01

    OBJECTIVE: The aim of this study was to investigate whether low-intensity extracorporeal shockwave therapy (LI-ESWT) can be used as a treatment for men with erectile dysfunction of organic origin. MATERIALS AND METHODS: This prospective, randomized, blinded, placebo-controlled study included 112 ...... are needed. KEYWORDS: Erectile dysfunction; extracorporeal shockwave; penis...

  19. Improvement of disfiguring skin conditions by laser therapy

    NARCIS (Netherlands)

    van Drooge, A.M.

    2014-01-01

    Since their introduction in dermatology, lasers became a welcome addition to the therapeutic armentarium for disfiguring skin conditions. In this thesis, we evaluated laser therapy for the treatment of scars, of benign dermal tumours, and of port-wine stains. For scars, many different laser devices

  20. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chuong, Michael D. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Hallemeier, Christopher L. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Jabbour, Salma K. [Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey (United States); Yu, Jen; Badiyan, Shahed [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Merrell, Kenneth W. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Mishra, Mark V. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Li, Heng [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Verma, Vivek [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska (United States); Lin, Steven H., E-mail: shlin@mdanderson.org [Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2016-05-01

    Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.

  1. [Herpetic infection in patients with psoriasis: the improvement of therapy].

    Science.gov (United States)

    Shul'diakov, A A; Barkhatova, T S; Satarova, S A; Perminova, T A

    2012-01-01

    The aim of the study was to estimate the efficacy of liniment cycloferon included in combined therapy of herpetic infection in 30 patients with psoriasis divided into 2 groups. Combined treatment of patients with recurrent herpetic infection promoted elimination of general infection syndrome, shortened duration of eruption and local inflammation, accelerated epithelization of herpetic erosion, and decreased the frequency of relapses during the follow-up.

  2. Improvement of disfiguring skin conditions by laser therapy

    OpenAIRE

    van Drooge, A.M.

    2014-01-01

    Since their introduction in dermatology, lasers became a welcome addition to the therapeutic armentarium for disfiguring skin conditions. In this thesis, we evaluated laser therapy for the treatment of scars, of benign dermal tumours, and of port-wine stains. For scars, many different laser devices have been proposed. In this thesis, we performed a review that showed the pulsed dye laser most effective in hypertrophic scars. We did not find enough evidence for the efficacy of ablative fractio...

  3. Improvement of herpetic stomatitis therapy in patients with chronic tonsillitis

    Directory of Open Access Journals (Sweden)

    Lepilin А.V.

    2011-12-01

    Full Text Available The research goal is to determine the clinical and pathogenetic efficacy of Cycloferon liniment in the combined therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis. Materials and methods: Medical examination and treatment of 60 patients have been carried out. The marker of endogenous intoxication, infectious severity and immunity has been investigated. Results. It has been established that use of Cycloferon liniment in the combined therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis has allowed to decrease infectious severity in par-odontal recess and evidence of local inflammation, to normalize immunity indices and reduce the level of endogenous intoxication that has been liable for acceleration of recuperation processes and lowering of frequency of stomatitis recurrences. Conclusion. The clinical efficacy of Cycloferon liniment in the therapy in patients with herpetic stomatitis accompanied by chronic tonsillitis conditioned by the decreasing of activity of local inflammatory process according to the reducing of level pro-inflammatory cytokines, infectious burden of the mouth cavity, endogenous intoxication

  4. [New methods of patient selection for improved anticholinergic therapy].

    Science.gov (United States)

    Neuhaus, J; Schwalenberg, T; Schlichting, N; Schulze, M; Horn, L-C; Stolzenburg, J-U

    2007-09-01

    M3-specific inhibitors are currently preferred for anticholinergic therapy of OAB. However, not all of the patients profit from this regimen. This might reflect a heterogeneity of the patient group. The aim of this work is to define subgroups of patients with specific alterations of receptor expression and to profile the receptor expression individually. These receptor profiles might be used for the development of evidence-based "tailored" therapies. Detrusor probes from bladder carcinoma patients (BCa, n=9 F, n=7 male) and interstitial cystitis patients (IC, n=9 female) were examined using confocal immunofluorescence and PCR. M2, M3, P2X1-3, and H1-3 mRNAs were demonstrated in detrusor tissue. As revealed by immunofluorescence, the M2 receptor expression was significantly higher in female compared to male BCa tissues. In addition, the M2 receptor was further upregulated in IC vs BCa in female detrusor. IC patients showed specific alterations of their receptor profile. Individual receptor profiles might be used to optimize medicinal therapies.

  5. Case Report: Improved Homonymous Hemianopia with Hyperbaric Oxygen Therapy

    Science.gov (United States)

    2017-06-29

    in the visual fields was noted at 13 treatments, but approximately 50% improvement was demonstrated in the right eye after 30 treatments with less...significant objective improvement of a fixed neurologic deficit following an ischemic brain injury. Various hypotheses exist regarding the recovery of

  6. Tailored cognitive-behavioural therapy and exercise training improves the physical fitness of patients with fibromyalgia

    NARCIS (Netherlands)

    Spillekom-van Koulil, S.; Lankveld, W.G.J.M. van; Kraaimaat, F.W.; Helmond, T. van; Vedder, A.; Hoorn, H. van; Donders, A.R.T.; Wirken, L.; Cats, H.; Riel, P.L.C.M. van; Evers, A.W.M.

    2011-01-01

    OBJECTIVES: Patients with fibromyalgia have diminished levels of physical fitness, which may lead to functional disability and exacerbating complaints. Multidisciplinary treatment comprising cognitive-behavioural therapy (CBT) and exercise training has been shown to be effective in improving

  7. Optimizing autologous cell grafts to improve stem cell gene therapy.

    Science.gov (United States)

    Psatha, Nikoletta; Karponi, Garyfalia; Yannaki, Evangelia

    2016-07-01

    Over the past decade, stem cell gene therapy has achieved unprecedented curative outcomes for several genetic disorders. Despite the unequivocal success, clinical gene therapy still faces challenges. Genetically engineered hematopoietic stem cells are particularly vulnerable to attenuation of their repopulating capacity once exposed to culture conditions, ultimately leading to low engraftment levels posttransplant. This becomes of particular importance when transduction rates are low or/and competitive transplant conditions are generated by reduced-intensity conditioning in the absence of a selective advantage of the transduced over the unmodified cells. These limitations could partially be overcome by introducing megadoses of genetically modified CD34(+) cells into conditioned patients or by transplanting hematopoietic stem cells hematopoietic stem cells with high engrafting and repopulating potential. On the basis of the lessons gained from cord blood transplantation, we summarize the most promising approaches to date of increasing either the numbers of hematopoietic stem cells for transplantation or/and their engraftability, as a platform toward the optimization of engineered stem cell grafts. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  8. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

    OpenAIRE

    Cideciyan, Artur V.; Jacobson, Samuel G.; Beltran, William A.; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J.; Olivares, Melani B.; Schwartz, Sharon B.; Komáromy, András M.; Hauswirth, William W.; Aguirre, Gustavo D.

    2013-01-01

    The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

  9. [Improvement of parodontitis therapy of patients with HIV-infection].

    Science.gov (United States)

    Soboleva, L A; Oseeva, A O; Shul'diakov, A A; Bulkina, N V

    2010-01-01

    For the purpose to determine the clinic-pathogenetic efficacy of cycloferon liniment in the combined therapy of periodontitis of patients with subclinical stage of HIV-infection medical examination and treatment of 40 patients was carried out. It was established that use of liniment cycloferon in the combined treatment of patients with subclinical stage of HIV-infection allowed to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood, to decrease infection load (herpes symplex virus I, Candida albicans, Staphylococcus aureus) in parodontal recess and evidence of local inflammation with reduction of activity of the tumours necrosis factor and interleukin 1beta, what provided acceleration of recuperation processes, lowering the frequency of parodontitis relapses.

  10. Adaptive mixed reality rehabilitation improves quality of reaching movements more than traditional reaching therapy following stroke.

    Science.gov (United States)

    Duff, Margaret; Chen, Yinpeng; Cheng, Long; Liu, Sheng-Min; Blake, Paul; Wolf, Steven L; Rikakis, Thanassis

    2013-05-01

    Adaptive mixed reality rehabilitation (AMRR) is a novel integration of motion capture technology and high-level media computing that provides precise kinematic measurements and engaging multimodal feedback for self-assessment during a therapeutic task. We describe the first proof-of-concept study to compare outcomes of AMRR and traditional upper-extremity physical therapy. Two groups of participants with chronic stroke received either a month of AMRR therapy (n = 11) or matched dosing of traditional repetitive task therapy (n = 10). Participants were right handed, between 35 and 85 years old, and could independently reach to and at least partially grasp an object in front of them. Upper-extremity clinical scale scores and kinematic performances were measured before and after treatment. Both groups showed increased function after therapy, demonstrated by statistically significant improvements in Wolf Motor Function Test and upper-extremity Fugl-Meyer Assessment (FMA) scores, with the traditional therapy group improving significantly more on the FMA. However, only participants who received AMRR therapy showed a consistent improvement in kinematic measurements, both for the trained task of reaching to grasp a cone and the untrained task of reaching to push a lighted button. AMRR may be useful in improving both functionality and the kinematics of reaching. Further study is needed to determine if AMRR therapy induces long-term changes in movement quality that foster better functional recovery.

  11. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

  12. Tamsulosin therapy improved the outcome of ureterorenoscopy for ...

    African Journals Online (AJOL)

    Introduction: Tamsulosin is an α-1A-specific blocker inducing selective relaxation of ureteral smooth muscle and inhibition of ureteral spasms leading to ureteral dilatation that can facilitates retrograde ureterorenoscopy (URS). Objective: To assess the efficacy of tamsulosin in improving the outcome of URS management of ...

  13. Corticosteroid therapy for duchenne muscular dystrophy: improvement of psychomotor function.

    Science.gov (United States)

    Sato, Yuko; Yamauchi, Akemi; Urano, Mari; Kondo, Eri; Saito, Kayoko

    2014-01-01

    Of the numerous clinical trials for Duchenne muscular dystrophy, only the corticosteroid prednisolone has shown potential for temporal improvement in motor ability. In this study, the effects of prednisolone on intellectual ability are examined in 29 cases of Duchenne muscular dystrophy because little information has been reported. And also, motor functions and cardiac functions were evaluated. The treated group was administered prednisolone (0.75 mg/kg) orally on alternate days and the compared with the untreated control group. Gene mutations were investigated. The patients were examined for intelligence quotient adequate for age, brain natriuretic peptide, creatine kinase, and manual muscle testing before treatment and after the period 6 months to 2 years. Intelligence quotient scores of the treated increased to 6.5 ± 11.9 (mean ± standard deviation) were compared with the controls 2.1 ± 4.9 (P = 0.009). Intelligence quotient scores of the patients with nonsense point mutations improved significantly (21.0 ± 7.9) more than those with deletion or duplication (1.9 ± 9.0; P = 0.015). Motor function, such as time to stand up, of those treated improved significantly and brain natriuretic peptide level was reduced to a normal level after treatment in 15 patients (73%). Our results demonstrate the effectiveness of prednisolone in improving intellectual impairment as well as in preserving motor function and brain natriuretic peptide levels. We presume that prednisolone has a read-through effect on the stop codons in the central nervous systems of Duchenne muscular dystrophy because intelligence quotient of point mutation case was improved significantly. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Cognitive behavioral therapy for suicidal behaviors: improving patient outcomes

    Directory of Open Access Journals (Sweden)

    Mewton L

    2016-03-01

    Full Text Available Louise Mewton,1 Gavin Andrews2 1National Health and Medical Research Council Centre for Research Excellence in Mental Health and Substance Use, National Drug and Alcohol Research Centre, University of New South Wales, 2Clinical Research Unit for Anxiety and Depression (CRUfAD, St Vincent's Hospital, Sydney, NSW, Australia Abstract: This systematic review provides an overview of the effectiveness of cognitive behavioral therapy (CBT in reducing suicidal cognitions and behavior in the adult population. We identified 15 randomized controlled trials of CBT for adults (aged 18 years and older that included suicide-related cognitions or behaviors as an outcome measure. The studies were identified from PsycINFO searches, reference lists, and a publicly available database of psychosocial interventions for suicidal behaviors. This review identified some evidence of the use of CBT in the reduction of both suicidal cognitions and behaviors. There was not enough evidence from clinical trials to suggest that CBT focusing on mental illness reduces suicidal cognitions and behaviors. On the other hand, CBT focusing on suicidal cognitions and behaviors was found to be effective. Given the current evidence, clinicians should be trained in CBT techniques focusing on suicidal cognitions and behaviors that are independent of the treatment of mental illness. Keywords: suicidal behaviors, suicidal cognitions, CBT

  15. SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Y [Procure Proton Therapy Center, Oklahoma City, OK (United States); Flanz, J [Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Mah, D [Procure Treatment Center, Somerset, NJ (United States); Pankuch, M; Kreydick, B [Northwestern Medicine Proton Center, Warrenville, IL (United States); Beltran, C [Mayo Clinic, Rochester, MN (United States); Robison, B; Schreuder, A [Provision Healthcare Partners, Knoxville, TN (United States)

    2016-06-15

    Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure mode and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.

  16. Improvement of cardiac function persists long term with medical therapy for left ventricular systolic dysfunction.

    Science.gov (United States)

    Chen, David; Chang, Richard; Umakanthan, Branavan; Stoletniy, Liset N; Heywood, J Thomas

    2007-09-01

    In certain patients with left ventricular (LV) systolic dysfunction, improvements in cardiac function are seen after initiation of medical therapy; however, the long-term stability of ventricular function in such patients is not well described. We retrospectively analyzed 171 patients who had a baseline ejection fraction of 45% or less, a follow-up echocardiogram at 2 to 12 months after initiation of medical therapy, and a final echocardiogram. We found that 48.5% of the patients demonstrated initial improvements in LV function after initiation of medical therapy, and the improvements appear to be sustained (88% of patients) at 44 +/- 21 months follow-up. A nonischemic etiology and younger age were the only independent predictors of change of LV ejection fraction of 10 or more at a mean 8.4 +/- 3.4 months after optimal medical therapy. Our study revealed a trend toward improved long-term survival in individuals with an early improvement in LV ejection fraction with medical therapy, especially in those with sustained improvement.

  17. Integrating Quality and Safety Competencies to Improve Outcomes: Application in Infusion Therapy Practice.

    Science.gov (United States)

    Sherwood, Gwen; Nickel, Barbara

    Despite intense scrutiny and process improvement initiatives, patient harm continues to occur in health care with alarming frequency. The Quality and Safety Education for Nursing (QSEN) project provides a roadmap to transform nursing by integrating 6 competencies: patient-centered care, teamwork and collaboration, evidence-based practice, quality improvement, safety, and informatics. As front-line caregivers, nurses encounter inherent risks in their daily work. Infusion therapy is high risk with multiple potential risks for patient harm. This study examines individual and system application of the QSEN competencies and the Infusion Nurses Society's 2016 Infusion Therapy Standards of Practice in the improvement of patient outcomes.

  18. Improved osteogenic vector for non-viral gene therapy

    Directory of Open Access Journals (Sweden)

    ARA Hacobian

    2016-03-01

    Full Text Available Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2 gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp. Transfection of multiple cell lines and rat adipose-derived mesenchymal stem cells with plasmids harbouring the improved BMP-2 sequence led to a several fold increased expression rate and subsequent osteogenic differentiation. Additionally, comparing expression kinetics of elongation factor 1 alpha (EF1α promoter with a state of the art CMV promoter revealed significantly higher BMP-2 expression when under the influence of the EF1α promoter. Results obtained by quantification of bone markers as well as osteogenic assays showed reduced sensitivity to promoter silencing effects of the EF1α promoter in rat adipose-derived mesenchymal stem cells. Finally, screening of several protein secretion signals using either luciferase or BMP-2 as reporter protein revealed no superior candidates for potential replacement of the native BMP-2 secretion signal. Taken together, by enhancing the exogenous BMP-2 expression system, low transfection efficiencies in therapeutic applications can be compensated, making safe non-viral systems even more suitable for tissue regeneration approaches.

  19. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

    Science.gov (United States)

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

    2010-06-01

    To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

  20. Reducing dysfunctional beliefs about sleep does not significantly improve insomnia in cognitive behavioral therapy.

    Science.gov (United States)

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the baseline and at the end of treatment. The results showed that although cognitive behavioral therapy for insomnia greatly reduced individuals' scores on both scales, the decrease in dysfunctional beliefs and attitudes about sleep with treatment did not seem to mediate improvement in insomnia. The findings suggest that sleep-related dysfunctional beliefs endorsed by patients with chronic insomnia may be attenuated by cognitive behavioral therapy for insomnia, but changes in such beliefs are not likely to play a crucial role in reducing the severity of insomnia.

  1. Improvement and decline in vision with gene therapy in childhood blindness.

    Science.gov (United States)

    Jacobson, Samuel G; Cideciyan, Artur V; Roman, Alejandro J; Sumaroka, Alexander; Schwartz, Sharon B; Heon, Elise; Hauswirth, William W

    2015-05-14

    Retinal gene therapy for Leber's congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss of photoreceptors in the treated retina was the same as that in the untreated retina. Here we describe long-term follow-up data from three treated patients. Topographic maps of visual sensitivity in treated regions, nearly 6 years after therapy for two of the patients and 4.5 years after therapy for the third patient, indicate progressive diminution of the areas of improved vision. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00481546.).

  2. Reducing Dysfunctional Beliefs about Sleep Does Not Significantly Improve Insomnia in Cognitive Behavioral Therapy

    OpenAIRE

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the...

  3. Rapid improvement of respiratory quality in asthmatic children after "assisted drainage" therapy

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2010-08-01

    Full Text Available Background  Whilst current asthma management is well-developed, there are still 5-10% uncontrolled asthma patients with unknown etiologies. However, its connection with oral focal infection is still uncertain. Therefore, a collaborated research for asthma management was conducted by pediatricians and dental practitioners. Within minutes after the "assisted drainage" therapy, a modification of healing root planning procedure, there is rapid improvement of respiratory function, ie., forced expiratory-volume one second (FEV1 in asthmatic children. This quick response usually achieved by oral inhalation. Objective To investigate the effectiveness of the assisted drainage therapy in the improvement of respiratory quality. Methods Fifteen asthmatic children were subjected to a longitudinal study for two weeks. In tbe first week they were instructed for al lergen avoidance only and the fOllowing one week was combined with tbe assisted drainage therapy, followed by  mental health education and dental plaque control therapy. Each s'ubject was af'sef'sed for respiratory quality with a computerized spirometer and blood sampling test. Paired t-test analysis was used for statistical analysis. Results Assisted drainage therapy was performed, within minutes FEV1 increased significantly (P= 0.001. Additionally, there were significant differences serum histamine (P= 0,001 pre and post treatment. Conclusions The assisted drainage therapy is effective as an adjuvant therapy for mild persistent asthma in children.

  4. Effect of neurofeedback and electromyographic-biofeedback therapy on improving hand function in stroke patients.

    Science.gov (United States)

    Rayegani, S M; Raeissadat, S A; Sedighipour, L; Rezazadeh, I Mohammad; Bahrami, M H; Eliaspour, D; Khosrawi, S

    2014-01-01

    The aim of the present study was to evaluate the effect of applying electroencephalogram (EEG) biofeedback (neurobiofeedback) or electromyographic (EMG) biofeedback to conventional occupational therapy (OT) on improving hand function in stroke patients. This study was designed as a preliminary clinical trial. Thirty patients with stroke were entered the study. Hand function was evaluated by Jebsen Hand Function Test pre and post intervention. Patients were allocated to 3 intervention cohorts: (1) OT, (2) OT plus EMG-biofeedback therapy, and (3) OT plus neurofeedback therapy. All patients received 10 sessions of conventional OT. Patients in cohorts 2 and 3 also received EMG-biofeedback and neurofeedback therapy, respectively. EMG-biofeedback therapy was performed to strengthen the abductor pollicis brevis (APB) muscle. Neurofeedback training was aimed at enhancing sensorimotor rhythm after mental motor imagery. Hand function was improved significantly in the 3 groups. The spectral power density of the sensorimotor rhythm band in the neurofeedback group increased after mental motor imagery. Maximum and mean contraction values of electrical activities of the APB muscle during voluntary contraction increased significantly after EMG-biofeedback training. Patients in the neurofeedback and EMG-biofeedback groups showed hand improvement similar to conventional OT. Further studies are suggested to assign the best protocol for neurofeedback and EMG-biofeedback therapy.

  5. Speech and language therapies to improve pragmatics and discourse skills in patients with schizophrenia.

    Science.gov (United States)

    Joyal, Marilyne; Bonneau, Audrey; Fecteau, Shirley

    2016-06-30

    Individuals with schizophrenia display speech and language impairments that greatly impact their integration to the society. The aim of this systematic review was to identify the importance of speech and language therapy (SLT) as part of rehabilitation curriculums for patients with schizophrenia emphasizing on the speech and language abilities assessed, the therapy setting and the therapeutic approach. This article reviewed 18 studies testing the effects of language therapy or training in 433 adults diagnosed with schizophrenia. Results showed that 14 studies out of 18 lead to improvements in language and/or speech abilities. Most of these studies comprised pragmatic or expressive discursive skills being the only aim of the therapy or part of it. The therapy settings vary widely ranging from twice daily individual therapy to once weekly group therapy. The therapeutic approach was mainly operant conditioning. Although the evidence tends to show that certain areas of language are treatable through therapy, it remains difficult to state the type of approach that should be favoured and implemented to treat language impairments in schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Bispecific Antibody Pretargeting for Improving Cancer Imaging and Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sharkey, Robert M.

    2005-02-04

    The main objective of this project was to evaluate pretargeting systems that use a bispecific antibody (bsMAb) to improve the detection and treatment of cancer. A bsMAb has specificity to a tumor antigen, which is used to bind the tumor, while the other specificity is to a peptide that can be radiolabeled. Pretargeting is the process by which the unlabeled bsMAb is given first, and after a sufficient time (1-2 days) is given for it to localize in the tumor and clear from the blood, a small molecular weight radiolabeled peptide is given. According to a dynamic imaging study using a 99mTc-labeled peptide, the radiolabeled peptide localizes in the tumor in less than 1 hour, with > 80% of it clearing from the blood and body within this same time. Tumor/nontumor targeting ratios that are nearly 50 times better than that with a directly radiolabeled Fab fragment have been observed (Sharkey et al., ''Signal amplification in molecular imaging by a multivalent bispecific nanobody'' submitted). The bsMAbs used in this project have been composed of 3 antibodies that will target antigens found in colorectal and pancreatic cancers (CEA, CSAp, and MUC1). For the ''peptide binding moiety'' of the bsMAb, we initially examined an antibody directed to DOTA, but subsequently focused on another antibody directed against a novel compound, HSG (histamine-succinyl-glycine).

  7. Arginase inhibition prevents the development of hypertension and improves insulin resistance in obese rats.

    Science.gov (United States)

    Peyton, Kelly J; Liu, Xiao-Ming; Shebib, Ahmad R; Johnson, Fruzsina K; Johnson, Robert A; Durante, William

    2018-04-27

    This study investigated the temporal activation of arginase in obese Zucker rats (ZR) and determined if arginase inhibition prevents the development of hypertension and improves insulin resistance in these animals. Arginase activity, plasma arginine and nitric oxide (NO) concentration, blood pressure, and insulin resistance were measured in lean and obese animals. There was a chronological increase in vascular and plasma arginase activity in obese ZR beginning at 8 weeks of age. The increase in arginase activity in obese animals was associated with a decrease in insulin sensitivity and circulating levels of arginine and NO. The rise in arginase activity also preceded the increase in blood pressure in obese ZR detected at 12 weeks of age. Chronic treatment of 8-week-old obese animals with an arginase inhibitor or L-arginine for 4 weeks prevented the development of hypertension and improved plasma concentrations of arginine and NO. Arginase inhibition also improved insulin sensitivity in obese ZR while L-arginine supplementation had no effect. In conclusion, arginase inhibition prevents the development of hypertension and improves insulin sensitivity while L-arginine administration only mitigates hypertension in obese animals. Arginase represents a promising therapeutic target in ameliorating obesity-associated vascular and metabolic dysfunction.

  8. 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

  9. Improving Access to Psychological Therapies (IAPT) - The Need for Radical Reform.

    Science.gov (United States)

    Scott, Michael J

    2018-02-01

    Improving Access to Psychological Therapies is a UK government-funded initiative to widen access to the psychological treatment of depression and anxiety disorders. The author has had the opportunity to independently assess 90 Improving Access to Psychological Therapies clients, using a standardised semi-structured interview, the Structured Clinical Diagnostic Interview for DSM Disorders (SCID) and to listen to their account of interaction with the service. The results suggest that only the tip of the iceberg fully recovers from their disorder (9.2%) whether or not they were treated before or after a personal injury claim. There is a pressing need to re-examine the modus operandi of the service.

  10. Evidence Supporting Intralesional Stem Cell Therapy to Improve Equine Flexor Tendon Healing

    Directory of Open Access Journals (Sweden)

    Sushmitha Durgam

    2017-01-01

    Full Text Available Clinical bottom lineCurrent experimental evidence suggests that intralesional stem cell administration improves the histological characteristics and matrix organisation of healing equine superficial digital flexor tendons (SDFT; however, the clinical relevance of these findings are not clear. Current case-based evidence suggests that cell-based therapies improve the quality of tendon healing and reduce the recurrence rates of SDFT injuries but the lack of any randomised, controlled prospective studies with function-based outcomes is still concerning, given the widespread advocacy for and use of ‘stem cell’ therapies for the treatment of equine tendon injuries. 

  11. WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  12. Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of Symptom Amelioration and Ischemia Improvement

    Directory of Open Access Journals (Sweden)

    Youko Takakuwa

    2018-01-01

    Full Text Available Objective(s: The current management of coronary artery disease (CAD relies on three major therapeutic options, namely medication, percutaneous coronary intervention (PCI, and coronary artery bypass grafting (CABG. However, severe CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW therapy reported on human for the first time. This treatment resulted in better myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy, angina symptoms, and exercise tolerance. The aim of the present study was to investigate myocardial perfusion images and evaluate the relationship between the ischemia improvement and symptom amelioration by SW therapy. Methods: We treated ten patients (i.e., nine males and one female with cardiac SW therapy who had CAD but not indicated for PCI or CABG and aged 63–89 years old. After the SW therapy, all patients were followed up for three months to evaluate any amelioration of the myocardial ischemia based on symptoms, adenosine stress thallium scintigraphy, transthoracic echocardiography, and blood biochemical examinations. Results: The changes in various parameters were evaluated before and after cardiac SW therapy. The cardiac SW therapy resulted in a significant improvement in the symptoms as evaluated by the Canadian Cardiovascular Society [CCS] class score (P=0.016 and a tendency to improve in summed stress score (SSS (P=0.068. However, no significant improvement was observed in the summed rest score (SRS, summed difference score (SDS, left ventricular wall motion score index (LVWMSI, N-terminal pro-brain natriuretic, and troponin I. The difference of CCS class score (ΔCCS was significantly correlated with those of SSS (ΔSSS and SDS (ΔSDS (r=0.69, P=0.028 and r=0.70, P=0.025, respectively. There was no significant correlation between ΔCCS and other parameters. Furthermore, no significant

  13. Effect of CPAP Therapy in Improving Daytime Sleepiness in Indian Patients with Moderate and Severe OSA.

    Science.gov (United States)

    Battan, Gulshan; Kumar, Sanjeev; Panwar, Ajay; Atam, Virendra; Kumar, Pradeep; Gangwar, Anil; Roy, Ujjawal

    2016-11-01

    Obstructive Sleep Apnoea (OSA) is a highly prevalent disease and a major public health issue in India. Excessive daytime sleepiness is an almost ubiquitous symptom of OSA. Epworth Sleepiness Scale (ESS) score is a validated objective score to measure the degree of daytime sleepiness. Continuous Positive Airway Pressure (CPAP) therapy has been established as the gold standard treatment modality for OSA patients. A few Indian studies have reported the effectiveness of CPAP therapy in improving ESS scores after 1 st month of CPAP use. To observe both, short-term (one month) and long-term (three month) effects of CPAP therapy on ESS scores in moderate to severe OSA patients. The patients complaining of excessive day-time sleepiness, snoring and choking episodes during sleep, consecutively presenting to medicine OPD over a period of 2 years, were subjected to Polysomnography (PSG). Seventy-three patients with apnoea-hypopnea index (AHI) ≥15 were categorised as having moderate to severe forms of OSA (moderate OSA with AHI=15-30 and severe OSA with AHI >30), and were scheduled for an initial trial of CPAP therapy. Forty-seven patients reported good tolerance to CPAP therapy after a trial period of 2 weeks and comprised the final study group. ESS scores in these patients were recorded at the baseline, and after 1 st and 3 rd month of CPAP therapy, and statistically analysed for significance. Mean ESS score at the baseline among moderate and severe OSA patients were 13.67±2.29 and 16.56 ±1.87, respectively. ESS score in both these subgroups improved significantly to 11.63±3.79, p=0.022, CI (0.3293-4.0106)} and 14.13 ±3.74, p CPAP therapy. Likewise, mean ESS scores among moderate and severe OSA patients improved significantly to 9.84 ±2.97, p = 0.022, CI (0.3293-4.0106) and 12.29 ±3.97, p CPAP therapy. The result of the present study shows that CPAP therapy is significantly effective in improving ESS scores in Indian patients having moderate to severe OSA. Benefits

  14. Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

    Science.gov (United States)

    Chien, Cheng-Hung; Lin, Chih-Lang; Hu, Ching-Chih; Chang, Jia-Jang; Chien, Rong-Nan

    2015-12-01

    Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

  15. Does Nursing Facility Use of Habilitation Therapy Improve Performance on Quality Measures?

    Science.gov (United States)

    Fitzler, Sandra; Raia, Paul; Buckley, Fredrick O; Wang, Mei

    2016-12-01

    The purpose of the project, Centers for Medicare & Medicaid Services (CMS) Innovation study, was to evaluate the impact on 12 quality measures including 10 Minimum Data Set (MDS) publicly reported measures and 2 nursing home process measures using habilitation therapy techniques and a behavior team to manage dementia-related behaviors. A prospective design was used to assess the changes in the measures. A total of 30 Massachusetts nursing homes participated in the project over a 12-month period. Project participation required the creation of an interdisciplinary behavior team, habilitation therapy training, facility visit by the program coordinator, attendance at bimonthly support and sharing calls, and monthly collection of process measure data. Participating facilities showed improvement in 9 of the 12 reported measures. Findings indicate potential quality improvement in having nursing homes learn habilitation therapy techniques and know how to use the interdisciplinary team to manage problem behaviors. © The Author(s) 2016.

  16. A Pharmaceutical Care Program to Improve Adherence to Statin Therapy : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Eussen, Simone R. B. M.; van der Elst, Menno E.; Klungel, Olaf H.; Rompelberg, Cathy J. M.; Garssen, Johan; Oosterveld, Marco H.; de Boer, Anthonius; de Gier, Johan J.; Bouvy, Marcel L.

    2010-01-01

    BACKGROUND: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. OBJECTIVE: To implement and assess the effectiveness of a community pharmacy based pharmaceutical care program developed to improve patients' adherence to statin therapy.

  17. Improvements in Behavioral Symptoms following Antibiotic Therapy in a 14-Year-Old Male with Autism

    Directory of Open Access Journals (Sweden)

    P. Lucas Ramirez

    2013-01-01

    Full Text Available This case report describes the benefits of antibiotic and antifungal therapy on behavior in a child with autism undergoing treatment for encopresis. Over the course of treatment, the child exhibited a reduction in aberrant behaviors, increased gastrointestinal function, and improved quality of life.

  18. Group Therapy for Improving Self-Esteem and Social Functioning of College Students with ADHD

    Science.gov (United States)

    Shaikh, Ayesha

    2018-01-01

    The present study examined the effectiveness of interpersonal group therapy designed to improve self-esteem and social functioning in college students with Attention-Deficit/Hyperactivity Disorder (ADHD). Participants with documented ADHD diagnoses completed self-report measures of self-esteem and social functioning at the initiation of the study,…

  19. Improvements in Behavioral Symptoms following Antibiotic Therapy in a 14-Year-Old Male with Autism

    OpenAIRE

    Ramirez, P. Lucas; Barnhill, Kelly; Gutierrez, Alan; Schutte, Claire; Hewitson, Laura

    2013-01-01

    This case report describes the benefits of antibiotic and antifungal therapy on behavior in a child with autism undergoing treatment for encopresis. Over the course of treatment, the child exhibited a reduction in aberrant behaviors, increased gastrointestinal function, and improved quality of life.

  20. TSL Family Therapy Followed by Improved Marital Quality and Reduced Oxidative Stress

    Science.gov (United States)

    Kim, Jae Yop; Kim, Dong Goo; Nam, Seok In

    2012-01-01

    Objectives: The current study evaluated the effectiveness of a form of family therapy developed in Korea. The "Thank you--Sorry--Love" (TSL) model was applied to a group of elderly retired men to improve the quality of their marriage and to reduce their stress. Methods: Thirty married retired Korean men were assigned to three groups.…

  1. Improving breast cancer outcome by preoperative systemic therapy and image-guided surgery

    NARCIS (Netherlands)

    Mieog, Jan Sven David

    2011-01-01

    This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that

  2. Efficacy of Adjunct In-Home Coaching to Improve Outcomes in Parent-Child Interaction Therapy

    Science.gov (United States)

    Timmer, Susan G.; Zebell, Nancy M.; Culver, Michelle A.; Urquiza, Anthony J.

    2010-01-01

    Objectives: The purpose of this study is to test whether increasing the exposure to coaching by adding an in-home component to clinic-delivered Parent-Child Interaction Therapy (PCIT) will increase the speed of parenting skill acquisition and show greater improvements in children's behaviors and parental stress. Methods: Seventy-three parent-child…

  3. Leukocytapheresis Therapy Improved Cholestasis in a Patient Suffering from Primary Sclerosing Cholangitis with Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Minoru Itou

    2009-04-01

    Full Text Available Primary sclerosing cholangitis (PSC is an autoimmune disease of the hepatobiliary system for which effective therapy has not been established. Leukocytapheresis (LCAP therapy is known to effective in patients with ulcerative colitis (UC. In addition, effects of LCAP therapy were reported on some autoimmune diseases such as Crohn’s disease, rheumatoid arthritis and rapidly progressive glomerulonephritis. Here we report the case of a 29-year-old man with PSC associated with UC who was treated with LCAP therapy. He had a 16-year history of UC and a 12-year history of PSC. Although he was under treatment with prednisolone and ursodeoxycholic acid, exacerbation of UC and PSC-associated cholestasis were seen. Since he showed side effects of prednisolone, he was treated with LCAP. Not only improvement of UC, but also decreased serum alkaline phosphatase, γ-guanosine triphosphate and total bile acids, suggesting improvement of PSC-associated cholestaisis, were seen after treatment with LCAP. Our experience with this case suggests that LCAP therapy could be a new effective therapeutic strategy for patients with PSC associated with UC.

  4. Survival improvement in patients with disseminated medullary thyroid carcinoma treated with 131I-MIBG therapy

    International Nuclear Information System (INIS)

    Mihaljevic, I.; Topuzovi, N.; Snajder, D.

    2015-01-01

    Full text of publication follows. Introduction and aim: The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of medullary thyroid carcinoma (MTC) with local and distant metastases. MTC is an uncommon thyroid tumor, accounting from 3-5% of all thyroid malignancies, and arises from para-follicular C cells which produce calcitonin (CT). Prognosis of MTC is related to tumor extension at disease detection, but long-term survival in patients with disseminated MTC is still unsatisfactory. Methods: 4 female patients with metastatic MTC (63, 69 and 2 patients aged 73 years), which already underwent total thyroidectomy and selective neck dissection, received therapy with 100 mCi 131 I-MIBG in our Institute. Patients had widespread disease with neck recurrences (all 4 cases), liver and bone metastases (2 cases) and lung metastases (1 case). All those patients received the therapy twice, second one 3 months up to 1 year after the first cycle. After therapy, whole body scintigraphy was performed; tumor marker levels (CT, carcinoembryonic antigen - CEA, neuron specific enolase - NSE, chromogranin A - CgA and pro-gastrin releasing peptide - pro-GRP) were measured before and after therapy. Results: in one patient we observed a slight decrease in CT level after first MIBG therapy, in another one a slight decrease in CEA serum level, and no lung metastases were visible on whole body scan after second 131 I-MIBG therapy. In one of the two remaining cases there was a significant decrease in CT serum level only after neck dissection. In all cases the patients reported an improvement in subjective symptom reduction. Conclusion: 131 I-MIBG therapy could provide additional benefit to patients with MTC and could improve overall survival, but more patient should be treated in order to define the true potential of the therapy. The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of

  5. The Efficacy of Equine-Assisted Activities and Therapies on Improving Physical Function.

    Science.gov (United States)

    Rigby, B Rhett; Grandjean, Peter W

    2016-01-01

    To summarize the physical benefits of therapeutic horseback riding and hippotherapy and suggest directions for future research. Review of databases for peer-reviewed articles related to equine-assisted activities and therapies. Databases included MEDLINE via EBSCO, Web of Science, PubMed, Google Scholar, and Academic Search Complete. Articles were limited to those with full-text access published in English since 1987. Acute and residual improvements in physical benefits, such as gross motor function (e.g., walking, running, jumping), spasticity, muscle symmetry, posture, balance, and gait occur in adults and children with varying disabilities. The benefits appear to be greatest following multiweek interventions with one or more sessions per week. Modest acute cardiovascular responses are observed during equine-assisted activities and therapies with little or no evidence for training improvements in heart rate or blood pressure at rest or during riding. The present body of literature provides evidence that equine-assisted activities and therapies are an effective means of improving many measures of physical health. However, more controlled trials are urgently needed to strengthen the current knowledge base, establish dose-response characteristics of equine-assisted activities and therapies, and explore the physiologic basis for the promising results suggested from the literature.

  6. Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer Therapy.

    Science.gov (United States)

    Kellner, Christian; Otte, Anna; Cappuzzello, Elisa; Klausz, Katja; Peipp, Matthias

    2017-09-01

    In the last two decades, monoclonal antibodies have revolutionized the therapy of cancer patients. Although antibody therapy has continuously been improved, still a significant number of patients do not benefit from antibody therapy. Therefore, rational optimization of the antibody molecule by Fc engineering represents a major area of translational research to further improve this potent therapeutic option. Monoclonal antibodies are able to trigger a variety of effector mechanisms. Especially Fc-mediated effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in antibody therapy of cancer. Novel mechanistic insights into the action of monoclonal antibodies allowed the development of various Fc engineering approaches to modulate antibodies' effector functions. Strategies in modifying the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering the protein backbone (Fc protein engineering) have been intensively evaluated. In the current review, Fc engineering strategies resulting in improved ADCC, ADCP and CDC activity are summarized and discussed.

  7. Objective evaluation of improvement in optic neuropathy following radiation therapy for thyroid eye disease

    International Nuclear Information System (INIS)

    Rush, Stephen; Winterkorn, Jacqueline; Zak, Rochelle

    2000-01-01

    Purpose: While the literature supports the use of radiation therapy for thyroid eye disease, it does not sufficiently describe in detail the results of radiation therapy for optic neuropathy associated with thyroid eye disease. The objective of this study is to quantify the changes in parameters of optic neuropathy after orbital irradiation for thyroid eye disease. Methods and Materials: Twelve consecutive patients with optic neuropathy from thyroid eye disease were followed by a single neuro-ophthalmology practice and treated by one radiation oncologist with radiation therapy from 1991 through 1995. All cases were prospectively followed for visual acuity, color vision, mean deviation, and/or foveal sensitivity and afferent pupillary defect. All patients received 2000 cGy in 10 fractions with megavoltage irradiation to the orbits. Results: Ten of 12 patients were evaluated for follow-up (one moved out of this country and one had a stroke, which confounded interpretation of examination results). An analysis was performed retrospectively while treatment and evaluation remained uniform. Five men and five women formed the basis of this study with a median age of 60 years (35-76 years). Nineteen eyes were evaluated for thyroid optic neuropathy. Improvement in optic nerve function occurred in eight of ten patients. Improvement was seen either during radiotherapy or within 2 weeks of completion. No long-term adverse effects were noted. Conclusion: This study objectively demonstrates improvement in optic neuropathy from radiation therapy for thyroid eye disease

  8. The ways of improvement of combination therapy results in patients with local cervical cancer

    International Nuclear Information System (INIS)

    Shumilo, A.O.

    2010-01-01

    A new solutions of a scientific task of modern oncogynecology, improvement of the efficacy of treatment for local cervical cancer on the account of expansion of the indications to operative treatment is presented on the clinical material (275 patients with stage II-III CC). The use of the developed technique of multimodality therapy based on the split course of combination radiation therapy against a background of neoadjuvant chemotherapy allowed to convert in 49.6% of cases of immobile tumor process to an operable stage followed by uterus and adnexae removal while at the traditional combination radiotherapy the resectability index was 6.9%.

  9. Designing the future of talking therapy: Using digital health to improve outcomes in psychosis

    Directory of Open Access Journals (Sweden)

    Amy Hardy

    2016-01-01

    A mobile app appears to be a feasible means of addressing barriers to access, uptake and adherence in talking therapies for psychosis, and may reduce costs and improve outcomes. Wellcome Trust funding has recently been obtained to investigate integrating wearable technology into the app, with the aim of increasing its sensitivity to user needs and further reducing processing demands. A Thinkthru digital platform is also being designed for use during therapy sessions and will be synchronised with the app. Further investigation of the platform and app’s potential to facilitate meaningful behaviour change is warranted, and a feasibility study and randomised controlled trial are planned.

  10. The use of discrete-event simulation modelling to improve radiation therapy planning processes.

    Science.gov (United States)

    Werker, Greg; Sauré, Antoine; French, John; Shechter, Steven

    2009-07-01

    The planning portion of the radiation therapy treatment process at the British Columbia Cancer Agency is efficient but nevertheless contains room for improvement. The purpose of this study is to show how a discrete-event simulation (DES) model can be used to represent this complex process and to suggest improvements that may reduce the planning time and ultimately reduce overall waiting times. A simulation model of the radiation therapy (RT) planning process was constructed using the Arena simulation software, representing the complexities of the system. Several types of inputs feed into the model; these inputs come from historical data, a staff survey, and interviews with planners. The simulation model was validated against historical data and then used to test various scenarios to identify and quantify potential improvements to the RT planning process. Simulation modelling is an attractive tool for describing complex systems, and can be used to identify improvements to the processes involved. It is possible to use this technique in the area of radiation therapy planning with the intent of reducing process times and subsequent delays for patient treatment. In this particular system, reducing the variability and length of oncologist-related delays contributes most to improving the planning time.

  11. Strategies to improve homing of mesenchymal stem cells for greater efficacy in stem cell therapy.

    Science.gov (United States)

    Naderi-Meshkin, Hojjat; Bahrami, Ahmad Reza; Bidkhori, Hamid Reza; Mirahmadi, Mahdi; Ahmadiankia, Naghmeh

    2015-01-01

    Stem/progenitor cell-based therapeutic approach in clinical practice has been an elusive dream in medical sciences, and improvement of stem cell homing is one of major challenges in cell therapy programs. Stem/progenitor cells have a homing response to injured tissues/organs, mediated by interactions of chemokine receptors expressed on the cells and chemokines secreted by the injured tissue. For improvement of directed homing of the cells, many techniques have been developed either to engineer stem/progenitor cells with higher amount of chemokine receptors (stem cell-based strategies) or to modulate the target tissues to release higher level of the corresponding chemokines (target tissue-based strategies). This review discusses both of these strategies involved in the improvement of stem cell homing focusing on mesenchymal stem cells as most frequent studied model in cellular therapies. © 2014 International Federation for Cell Biology.

  12. High Flow Nasal Cannula Therapy for Improving Obstructive Sleep Apnea: A Case Report

    Directory of Open Access Journals (Sweden)

    Se Joong Kim

    2015-06-01

    Full Text Available Although continuous positive airway pressure is the treatment of choice for obstructive sleep apnea, its compliance is low. Therefore, alternative therapeutic strategies are often required. High flow nasal cannula therapy uses an air compressor to deliver a constant flow of oxygen via the nasal cannula at a maximum of 60 L/m. It can produce positive end expiratory pressure and increase end expiratory pharyngeal pressure, which can help to alleviate upper airway obstruction. This is a case report of high flow nasal cannula therapy for a 71 year-old man. He had an obstructive sleep apnea and severe desaturation but failed to use continuous positive airway pressure. He underwent titration with high flow nasal cannula under polysomnography. Using high flow nasal cannula at an airflow of 45 L/m, his apnea-hypopnea, respiratory arousal and oxygen desaturation were improved. Importantly, he is very compliant with high flow nasal cannula therapy.

  13. Human gene therapy: novel approaches to improve the current gene delivery systems.

    Science.gov (United States)

    Cucchiarini, Magali

    2016-06-01

    Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.

  14. Effectiveness of Animal Assisted Therapy after brain injury: A bridge to improved outcomes in CRT.

    Science.gov (United States)

    Stapleton, Mary

    2016-06-18

    Animal Assisted Therapy (AAT) has been widely used as a complementary therapy in mental health treatment especially to remediate social skill deficits. The goal of AAT is to improve social, emotional, and cognitive functioning. The purpose of this article is to draw upon the literature on AAT and explore specific applications to cognitive rehabilitation therapy (CRT) and social skills training. This study provides a systematic review of most of the available literature on ATT and assesses that potential uses of ATT for brain injury rehabilitation. Although the efficacy of AAT is not currently well documented by rigorous research, (Kazin, 2010) anecdotal evidence suggests that brain injury survivors may benefit from the combination of AAT and cognitive rehabilitation techniques. Acquired Brain Injury (ABI) survivors with cognitive impairments can benefit from AAT as part of a comprehensive and holistic rehabilitation treatment plan.

  15. A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

    Science.gov (United States)

    Nakamura, Makiko; Sunagawa, Osahiko; Hokama, Ryo; Tsuchiya, Hiroyuki; Miyara, Takafumi; Taba, Yoji; Touma, Takashi

    2016-09-28

    The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.

  16. CPAP therapy improves erectile function in patients with severe obstructive sleep apnea.

    Science.gov (United States)

    Schulz, Richard; Bischof, Fabian; Galetke, Wolfgang; Gall, Henning; Heitmann, Jörg; Hetzenecker, Andrea; Laudenburg, Markus; Magnus, Till Jonas; Nilius, Georg; Priegnitz, Christina; Randerath, Winfried; Schröder, Maik; Treml, Marcel; Arzt, Michael

    2018-04-10

    Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients. Ninety-four men with severe OSA (ie, with an apnea-hypopnea-index ≥ 30/h of sleep) were prospectively evaluated for the presence and severity of ED before and after 6-12 months of CPAP therapy. The abbreviated version of the International Index of Erectile Function, (the IIEF-5) was used to rate erectile function. Furthermore, all study participants responded to standard questionnaires of daytime sleepiness (Epworth Sleepiness Scale), quality of life (WHO Wellbeing 5 questionnaire) and depression (Major Depression Inventory). ED as defined by an IIEF-5 score of ≤21 was present in 64 patients (68.1%). CPAP treatment significantly improved erectile function in those patients suffering from moderate and severe ED. Additionally, a trend for a correlation between the improvement of erectile function under CPAP and the hours of its use was observed. Finally, this effect was associated with larger improvements of quality of life in affected patients. ED is very frequent in men with severe OSA and can at least partly be reversed by long-term CPAP therapy in most seriously affected patients. The beneficial effect on erectile function may depend on CPAP compliance and is accompanied by improvements of quality of life. Randomized controlled trials are needed to confirm these findings. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Improvements in closeness, communication, and psychological distress mediate effects of couple therapy for veterans.

    Science.gov (United States)

    Doss, Brian D; Mitchell, Alexandra; Georgia, Emily J; Biesen, Judith N; Rowe, Lorelei Simpson

    2015-04-01

    Empirically based couple therapy results in significant improvements in relationship satisfaction for the average couple; however, further research is needed to identify mediators that lead to change and to ensure that improvements in mediators predict subsequent-not just concurrent-relationship satisfaction. In addition, given that much of the current literature on couple therapy examines outcomes in a research environment, it is important to examine mediators in a treatment-as-usual setting. To address these questions, 161 heterosexual couples (322 individuals) received treatment-as-usual couple therapy at one of two Veteran Administration Medical Centers (M = 5.0 and 13.0 sessions at the two sites) and were assessed before every session. The majority of couples were married (85%) and had been together for a median of 7.8 years (SD = 13). Participants were primarily White, non-Hispanic (69%), African American (21%), and White, Hispanic/Latino (8%). Individuals' own self-reported improvements in communication, emotional closeness, and psychological distress (but not frequency of behaviors targeted in treatment) mediated the effect of treatment on their subsequent relationship satisfaction. When all significant mediators were examined simultaneously, improvements in men's and women's emotional closeness and men's psychological distress independently mediated subsequent relationship satisfaction. In contrast, improvements in earlier relationship satisfaction mediated the effect of treatment only on subsequent psychological distress. This study identifies unique mediators of treatment effects and shows that gains in mechanisms predict subsequent relationship satisfaction. Future investigations should focus on the role of emotional closeness and psychological distress-constructs that have often been neglected-in couple therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  18. Manual Therapy and Exercise to Improve Outcomes in Patients With Muscle Tension Dysphonia: A Case Series

    Science.gov (United States)

    Archer, Kristin R.

    2015-01-01

    Background and Purpose Muscle tension dysphonia (MTD), a common voice disorder that is not commonly referred for physical therapy intervention, is characterized by excessive muscle recruitment, resulting in incorrect vibratory patterns of vocal folds and an alteration in voice production. This case series was conducted to determine whether physical therapy including manual therapy, exercise, and stress management education would be beneficial to this population by reducing excess muscle tension. Case Description Nine patients with MTD completed a minimum of 9 sessions of the intervention. Patient-reported outcomes of pain, function, and quality of life were assessed at baseline and the conclusion of treatment. The outcome measures were the numeric rating scale (NRS), Patient-Specific Functional Scale (PSFS), and Voice Handicap Index (VHI). Cervical and jaw range of motion also were assessed at baseline and postintervention using standard goniometric measurements. Outcomes Eight of the patients had no pain after treatment. All 9 of the patients demonstrated an improvement in PSFS score, with 7 patients exceeding a clinically meaningful improvement at the conclusion of the intervention. Three of the patients also had a clinically meaningful change in VHI scores. All 9 of the patients demonstrated improvement in cervical flexion and lateral flexion and jaw opening, whereas 8 patients improved in cervical extension and rotation postintervention. Discussion The findings suggest that physical therapists can feasibly implement an intervention to improve outcomes in patients with MTD. However, a randomized clinical trial is needed to confirm the results of this case series and the efficacy of the intervention. A clinical implication is the expansion of physical therapy to include referrals from voice centers for the treatment of MTD. PMID:25256740

  19. Improvement of sexual function in men with benign prostatic hyperplasia by pharmacologic therapy

    Directory of Open Access Journals (Sweden)

    Stojanović Nebojša

    2014-01-01

    Full Text Available Introduction. Benign prostatic hyperplasia (BPH causes disorders of voiding and sexual function. Pharmacologic therapy reduces symptoms of voiding thus impacting sexual function. Objective. To determine sex life status in men with BPH before and after pharmacologic treatment adapted to achieve satisfactory sexual function. Methods. We studied 117 sexually active BPH patients, not previously treated for BPH. After clinical examinations, symptoms of voiding, sexual and ejaculatory function were measured using standardized IPSS, IIEF and MSHQ-EjD questionnaires. After obtaining patients’ personal opinion about the importance of their sex life, therapy was chosen and possible side effects explained. Three groups of 39 patients each were formed. The first group was treated with alpha-blocker, tamsulosin, the second with 5-alpha reductase inhibitor, finasteride, while the third group was administered a combination therapy. The complete examination procedure was repeated after 3 and 6 months of therapy. Results. The average age of patients was 61.34±3.04 years. Eighty-seven percent reported that their sex life was important to a certain degree. Satisfaction with their sex life was reported by 47% of patients before treatment and by 67% of respondents 6 months after treatment. Questionnaire scores indicated general improvement of sexual function in all groups, which was statistically significant compared to baseline only in the group on tamsulosin alpha-blocker (2.95±7.81; p=0.028. The overall satisfaction with sex life as a component of sexual function, improved significantly in the group on the combined therapy (0.78±1.81; p=0.012. Conclusion. Before BPH treatment sexual function should be assessed and therapy customized to the patient’s expectations. Side effects of drugs should be presented especially to patients who emphasize the importance of sex life. In the manifested stages of the disease overall satisfaction with sex life may be

  20. Endostatin improves radioresponse and blocks tumor revascularization after radiation therapy for A431 xenografts in mice

    International Nuclear Information System (INIS)

    Itasaka, Satoshi; Komaki, Ritsuko; Herbst, Roy S.; Shibuya, Keiko; Shintani, Tomoaki D.D.S.; Hunter, Nancy R. M.S.; Onn, Amir; Bucana, Corazon D.; Milas, Luka; Ang, K. Kian; O'Reilly, Michael S.

    2007-01-01

    Purpose: Clinical trials of antiangiogenic agents used alone for advanced malignancy have been disappointing but preclinical studies suggest that the addition of radiation therapy could improve antitumor efficacy. To test the hypothesis that antiangiogenic therapy combined with radiation therapy can overcome the limitations of antiangiogenic monotherapy, we studied the effects of endostatin combined with radiation on the growth and vascularization of A431 human epidermoid carcinomas growing intramuscularly in the legs of mice. Methods and Materials: Mice with established A431 human epidermoid leg tumors were treated with radiation, endostatin, both radiation and endostatin, or vehicle control. The experiment was repeated and mice from each group were killed at 2, 7, and 10 days after irradiation so that tumor tissue could be obtained to further analyze the kinetics of the antitumor, antivascular, and antiangiogenic response to therapy. Results: Endostatin enhanced the antitumor effects of radiation, and prolonged disease-free survival was observed in the combined treatment group. Endothelial cell proliferation was increased in tumors after irradiation but was blocked by the concurrent administration of endostatin, and the combination of endostatin with radiation enhanced endothelial cell apoptosis within 48 h after irradiation. Expression of vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 were increased in tumors after irradiation, and this increase was blocked by concurrent administration of endostatin. Conclusion: These data indicate that endostatin can block tumor revascularization after radiation therapy and thereby augment radioresponse

  1. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

    Science.gov (United States)

    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  2. Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

    Science.gov (United States)

    Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

    2017-04-01

    An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

  3. The role of music therapy in rehabilitation: improving aphasia and beyond.

    Science.gov (United States)

    Leonardi, Simona; Cacciola, Alberto; De Luca, Rosaria; Aragona, Bianca; Andronaco, Veronica; Milardi, Demetrio; Bramanti, Placido; Calabrò, Rocco Salvatore

    2018-01-01

    Music is part of the human nature, and it is also philogenically relevant to language evolution. Language and music are bound together in the enhancement of important social functions, such as communication, cooperation and social cohesion. In the last few years, there has been growing evidence that music and music therapy may improve communication skills (but not only) in different neurological disorders. One of the plausible reasons concerning the rational use of sound and music in neurorehabilitation is the possibility to stimulate brain areas involved in emotional processing and motor control, such as the fronto-parietal network. In this narrative review, we are going to describe the role of music therapy in improving aphasia and other neurological disorders, underlying the reasons why this tool could be effective in rehabilitative settings, especially in individuals affected by stroke.

  4. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    Science.gov (United States)

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-03

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. 2011 Elsevier B.V. All rights reserved.

  5. Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease.

    Science.gov (United States)

    Holfeld, Johannes; Zimpfer, Daniel; Albrecht-Schgoer, Karin; Stojadinovic, Alexander; Paulus, Patrick; Dumfarth, Julia; Thomas, Anita; Lobenwein, Daniela; Tepeköylü, Can; Rosenhek, Raphael; Schaden, Wolfgang; Kirchmair, Rudolf; Aharinejad, Seyedhossein; Grimm, Michael

    2016-12-01

    Previously we have shown that epicardial shock-wave therapy improves left ventricular ejection fraction (LVEF) in a rat model of myocardial infarction. In the present experiments we aimed to address the safety and efficacy of epicardial shock-wave therapy in a preclinical large animal model and to further evaluate mechanisms of action of this novel therapy. Four weeks after left anterior descending (LAD) artery ligation in pigs, the animals underwent re-thoracotomy with (shock-wave group, n = 6) or without (control group, n = 5) epicardial shock waves (300 impulses at 0.38 mJ/mm 2 ) applied to the infarcted anterior wall. Efficacy endpoints were improvement of LVEF and induction of angiogenesis 6 weeks after shock-wave therapy. Safety endpoints were haemodynamic stability during treatment and myocardial damage. Four weeks after LAD ligation, LVEF decreased in both the shock-wave (43 ± 3%, p wave animals 6 weeks after treatment (62 ± 9%, p = 0.006); no improvement was observed in controls (41 ± 4%, p = 0.36), yielding a significant difference. Quantitative histology revealed significant angiogenesis 6 weeks after treatment (controls 2 ± 0.4 arterioles/high-power field vs treatment group 9 ± 3; p = 0.004). No acute or chronic adverse effects were observed. As a potential mechanism of action in vitro experiments showed stimulation of VEGF receptors after shock-wave treatment in human coronary artery endothelial cells. Epicardial shock-wave treatment in a large animal model of ischaemic heart failure exerted a positive effect on LVEF improvement and did not show any adverse effects. Angiogenesis was induced by stimulation of VEGF receptors. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Embracing technology? Using change management strategies to improve the use of continuous lateral rotation therapy.

    Science.gov (United States)

    Cybulski, Pamela; Zantinge, Johanna; Abbott-McNeil, Deanna

    2006-01-01

    The purpose of this quality improvement initiative was to improve the utilization of continuous lateral rotation therapy (CLRT) in a nine-bed community hospital ICU within the context of a nurse-driven protocol. Nursing focus groups, analyzed using a strength, weakness, opportunity, threat (SWOT) approach, resulted in the implementation of four interventions over seven weeks. Change management strategies guided all aspects of the project. Results showed a modest increase in the utilization of CLRT. This initiative demonstrates that change management strategies may assist with the incorporation of technology into nursing practice by increasing empowerment and creating an attachment to and responsibility for outcomes.

  7. Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans.

    Science.gov (United States)

    Brunt, Vienna E; Howard, Matthew J; Francisco, Michael A; Ely, Brett R; Minson, Christopher T

    2016-09-15

    A recent 30 year prospective study showed that lifelong sauna use reduces cardiovascular-related and all-cause mortality; however, the specific cardiovascular adaptations that cause this chronic protection are currently unknown. We investigated the effects of 8 weeks of repeated hot water immersion ('heat therapy') on various biomarkers of cardiovascular health in young, sedentary humans. We showed that, relative to a sham group which participated in thermoneutral water immersion, heat therapy increased flow-mediated dilatation, reduced arterial stiffness, reduced mean arterial and diastolic blood pressure, and reduced carotid intima media thickness, with changes all on par or greater than what is typically observed in sedentary subjects with exercise training. Our results show for the first time that heat therapy has widespread and robust effects on vascular function, and as such, could be a viable treatment option for improving cardiovascular health in a variety of patient populations, particularly those with limited exercise tolerance and/or capabilities. The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Intermittent hot water immersion ('heat therapy') results in elevations in core temperature and changes in cardiovascular haemodynamics, such as cardiac output and vascular shear stress, that are similar to exercise, and thus may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and/or capabilities. We sought to comprehensively assess the effects of 8 weeks of heat therapy on biomarkers of vascular function in young, sedentary subjects. Twenty young, sedentary subjects were assigned to participate in 8 weeks (4-5 times per week) of heat therapy (n = 10; immersion in a 40.5°C bath sufficient to maintain rectal temperature ≥ 38.5°C for 60 min per session) or thermoneutral water

  8. Improved Beam Angle Arrangement in Intensity Modulated Proton Therapy Treatment Planning for Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Cao, Wenhua; Lim, Gino J.; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

    2015-01-01

    Purpose: This study investigates potential gains of an improved beam angle arrangement compared to a conventional fixed gantry setup in intensity modulated proton therapy (IMPT) treatment for localized prostate cancer patients based on a proof of principle study. Materials and Methods: Three patients with localized prostate cancer retrospectively selected from our institution were studied. For each patient, IMPT plans were designed using two, three and four beam angles, respectively, obtained from a beam angle optimization algorithm. Those plans were then compared with ones using two lateral parallel-opposed beams according to the conventional planning protocol for localized prostate cancer adopted at our institution. Results: IMPT plans with two optimized angles achieved significant improvements in rectum sparing and moderate improvements in bladder sparing against those with two lateral angles. Plans with three optimized angles further improved rectum sparing significantly over those two-angle plans, whereas four-angle plans found no advantage over three-angle plans. A possible three-beam class solution for localized prostate patients was suggested and demonstrated with preserved dosimetric benefits because individually optimized three-angle solutions were found sharing a very similar pattern. Conclusions: This study has demonstrated the potential of using an improved beam angle arrangement to better exploit the theoretical dosimetric benefits of proton therapy and provided insights of selecting quality beam angles for localized prostate cancer treatment

  9. Can therapy dogs improve pain and satisfaction after total joint arthroplasty? A randomized controlled trial.

    Science.gov (United States)

    Harper, Carl M; Dong, Yan; Thornhill, Thomas S; Wright, John; Ready, John; Brick, Gregory W; Dyer, George

    2015-01-01

    % CI of risk ratio, 1.1-1.6]; risk difference, 18% [95% CI of risk difference, 5%-39%]). The overall hospital rating also was greater in the treatment group (0-10 scale) (9.6; SD, 0.7 [95% CI, 9.3-9.8] versus 8.6, SD, 0.9 [95% CI, 8.3-8.9], panimal-assisted therapy programs in their hospital as this may provide a means to improve the immediate postoperative recovery for a select group of patients having total joint arthroplasty. Level II, randomized controlled study. See Instructions for Authors for a complete description of levels of evidence.

  10. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    Directory of Open Access Journals (Sweden)

    Scanlon ML

    2013-01-01

    Full Text Available Michael L Scanlon,1,2 Rachel C Vreeman1,21Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; 2USAID, Academic Model Providing Access to Healthcare (AMPATH Partnership, Eldoret, KenyaAbstract: The rollout of antiretroviral therapy (ART significantly reduced human immunodeficiency virus (HIV-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a

  11. Improvement of quality of life following 6 months of methadone maintenance therapy in Malaysia.

    Science.gov (United States)

    Baharom, Nizam; Hassan, Mohd Rohaizat; Ali, Norsiah; Shah, Shamsul Azhar

    2012-08-01

    Methadone Maintenance Therapy (MMT) is one of the popular choices for drug substitution therapy and is fairly new in Malaysia. Aside from its role in harm reduction against HIV infection, MMT programme may potentially enhances clients' quality of life. This study aims to identify the impact of MMT programme on clients' quality of life after 6 months in treatment and to explore factors that may be associated with changes in their quality of life. In this retrospective report review, 122 subjects from 2 government MMT clinics were selected from the district of Tampin, Negeri Sembilan, Malaysia. The raw score from the WHO Quality of Life questionnaire (WHOQOL-BREF), at baseline and 6 months after therapy were collected and converted to 0-100 scale form to give quality of life scores for four domains; physical, psychological, social relationships and environment. Other variables of interest were socio-demography, age when joining MMT programme, age and duration of illicit drug use, HIV and Hepatitis C status, and the Opiate Treatment Index (OTI) score on drug use, sexual and social aspect at the baseline. Statistical analysis used the SPSS version 16. There was significant improvement in all four domains of quality of life, after 6 months of MMT. The largest improvement was for psychological domain (mean score difference 15.54 ± 20.81). Multivariable linear regression analysis showed that, for the physical domain, there was no significant predictor. For both the psychological and social domains, having tertiary education is a significant predictor for improvement in both aspects of quality of life. Negative HIV status is associated with improvement for the environment domain. There was a significant short term improvement in the quality of life of MMT clients who stayed in the programme for at least 6 months in the district of Tampin, Negeri Sembilan, Malaysia.

  12. Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

    Science.gov (United States)

    Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

    2018-02-01

    The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

  13. Self-Expanding Metal Stents Improve Swallowing and Maintain Nutrition During Neoadjuvant Therapy for Esophageal Cancer.

    Science.gov (United States)

    Smith, Zachary L; Gonzaga, Jason E; Haasler, George B; Gore, Elizabeth M; Dua, Kulwinder S

    2017-06-01

    Patients with locally advanced esophageal cancer can have significant dysphagia. Nutritional support during neoadjuvant therapy is often delivered via nasoenteric or percutaneous feeding tubes. These approaches do not allow for per-oral feeding. Evaluate the safety and efficacy of fully covered self-expanding metal esophageal stents for nutritional support during neoadjuvant therapy. This was a pilot, prospective study at a single tertiary center. From March 2012 to May 2013, consecutive patients with esophageal cancer eligible for neoadjuvant therapy were enrolled. Metal stents were placed prior to starting neoadjuvant therapy. Data were collected at baseline and predetermined intervals until an endpoint (surgery or disease progression). Outcomes included dysphagia grade, satisfaction of swallowing score, nutritional status (weight, serum albumin), impact on surgery, and adverse events. Fourteen stents were placed in 12 patients (59.1 ± 9.5 years, 11 men, 1 woman). Dysphagia grade (pre 3.4 ± 0.5 vs post 0.2 ± 0.4, p esophageal cancer, self-expanding metal stents are safe and effective in relieving dysphagia and maintaining nutrition. They allow patients to eat orally, thereby improving patient satisfaction. The presence of an in situ stent did not interfere with surgery.

  14. Effectiveness of Cognitive and Transactional Analysis Group Therapy on Improving Conflict-Solving Skill

    Directory of Open Access Journals (Sweden)

    Bahram A. Ghanbari-Hashemabadi

    2012-03-01

    Full Text Available Background: Today, learning the communication skills such as conflict solving is very important. The purpose of the present study was to investigate the efficiency of cognitive and transactional analysis group therapy on improving the conflict-solving skill.Materials and Method: This study is an experimental study with pretest-posttest and control group. Forty-five clients who were referring to the counseling and psychological services center of Ferdowsi University of Mashhad were chosen based on screening method. In addition, they were randomly divided into three equal groups: control group (15 participants, cognitive experimental group (15 participants and transactional analysis group (15 participants. Conflict-solving questionnaire was used to collect data and the intervention methods were cognitive and transactional analysis group therapy that was administrated during 8 weekly two-hour sessions. Mean and standard deviation were used for data analysis in the descriptive level and One-Way ANOVA method was used at the inference level.Results: The results of the study suggest that the conflict-solving skills in the two experimental groups were significantly increased. Conclusion: The finding of this research is indicative of the fact that both cognitive and transactional analysis group therapy could be an effective intervention for improving conflict-solving skills

  15. Interactive rehabilitation system for improvement of balance therapies in people with cerebral palsy.

    Science.gov (United States)

    Jaume-i-Capó, Antoni; Martínez-Bueso, Pau; Moyà-Alcover, Biel; Varona, Javier

    2014-03-01

    The present study covers a new experimental system, designed to improve the balance and postural control of adults with cerebral palsy. This system is based on a serious game for balance rehabilitation therapy, designed using the prototype development paradigm and features for rehabilitation with serious games: feedback, adaptability, motivational elements, and monitoring. In addition, the employed interaction technology is based on computer vision because motor rehabilitation consists of body movements that can be recorded, and because vision capture technology is noninvasive and can be used for clients who have difficulties in holding physical devices. Previous research has indicated that serious games help to motivate clients in therapy sessions; however, there remains a paucity of clinical evidence involving functionality. We rigorously evaluated the effects of physiotherapy treatment on balance and gait function of adult subjects with cerebral palsy undergoing our experimental system. A 24-week physiotherapy intervention program was conducted with nine adults from a cerebral palsy center who exercised weekly in 20-min sessions. Findings demonstrated a significant increase in balance and gait function scores resulting in indicators of greater independence for our participating adults. Scores improved from 16 to 21 points in a scale of 28, according to the Tinetti Scale for risk of falls, moving from high fall risk to moderate fall risk. Our promising results indicate that our experimental system is feasible for balance rehabilitation therapy.

  16. Aerobic Exercise as an Adjunct Therapy for Improving Cognitive Function in Heart Failure

    Directory of Open Access Journals (Sweden)

    Rebecca A. Gary

    2014-01-01

    Full Text Available Persons with heart failure (HF are typically older and are at a much higher risk for developing cognitive impairment (CI than persons without HF. Increasingly, CI is recognized as a significant, independent predictor of worse clinical outcomes, more frequent hospital readmissions, and higher mortality rates in persons with HF. CI can have devastating effects on ability to carry out HF effective self-care behaviors. If CI occurs, however, there are currently no evidence based guidelines on how to manage or improve cognitive function in this population. Improvement in cognition has been reported following some therapies in HF and is thought to be the consequence of enhanced cerebral perfusion and oxygenation, suggesting that CI may be amenable to intervention. Because there is substantial neuronal loss with dementia and no effective restorative therapies, interventions that slow, reverse, or prevent cognitive decline are essential. Aerobic exercise is documented to increase cerebral perfusion and oxygenation by promoting neuroplasticity and neurogenesis and, in turn, cognitive functioning. Few studies have examined exercise as a potential adjunct therapy for attenuating or alleviating cognitive decline in HF. In this review, the potential benefit of aerobic exercise on cognitive functioning in HF is presented along with future research directions.

  17. Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

    Science.gov (United States)

    Callan, Mary Beth; Haskins, Mark E; Wang, Ping; Zhou, Shangzhen; High, Katherine A; Arruda, Valder R

    2016-01-01

    Severe hemophilia A (HA) is an inherited bleeding disorder characterized by dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

  18. Improvement of JCDS, a computational dosimetry system in JAEA for neutron capture therapy

    International Nuclear Information System (INIS)

    Kumada, Hiroaki; Yamamoto, Kazuyoshi; Matsumura, Akira; Yamamoto, Tetsuya; Nakagawa, Yoshinobu; Kageji, Teruyoshi

    2006-01-01

    JCDS, a computational dosimetry system for neutron capture therapy, was developed by Japan Atomic Energy Agency. The system has been sophisticated to facilitate dose planning so far. In dosimetry with JCDS for BNCT clinical trials at JRR-4, several absorbed doses and the dose distributions are determined by a voxel model consisted of 2x2x2mm 3 voxel cells. By using the detailed voxel model, accuracy of the dosimetry can be improved. Clinical trials for melanoma and head-and-neck cancer as well as brain tumor were started using hot version of JCDS in 2005. JCDS is also being of improved so as to enable a JCDS application to dosimetry by PHITS as well as dosimetry by MCNP. By using PHITS, total doses of a patient by a combined modality therapy, for example a combination of BNCT and proton therapy, can be estimated consistently. Moreover, PET images can be adopted in combination with CT and MRI images as a farsighted approach. JCDS became able to identify target regions by using the PET values. (author)

  19. Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

    Directory of Open Access Journals (Sweden)

    Mary Beth Callan

    Full Text Available Severe hemophilia A (HA is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

  20. Improvement of the Oracle setup and database design at the Heidelberg ion therapy center

    International Nuclear Information System (INIS)

    Hoeppner, K.; Haberer, T.; Mosthaf, J.M.; Peters, A.; Thomas, M.; Welde, A.; Froehlich, G.; Juelicher, S.; Schaa, V. R.W.; Schiebel, W.; Steinmetz, S.

    2012-01-01

    The HIT (Heidelberg Ion Therapy) center is an accelerator facility for cancer therapy using both carbon ions and protons, located at the university hospital in Heidelberg. It provides three therapy treatment rooms: two with fixed beam exit (both in clinical use), and a unique gantry with a rotating beam head, currently under commissioning. The backbone of the proprietary accelerator control system consists of an Oracle database running on a Windows server, storing and delivering data of beam cycles, error logging, measured values, and the device parameters and beam settings for about 100,000 combinations of energy, beam size and particle rate used in treatment plans. Since going operational, we found some performance problems with the current database setup. Thus, we started an analysis that focused on the following topics: hardware resources of the database server, configuration of the Oracle instance, and a review of the database design that underwent several changes since its original design. The analysis revealed issues on all fields. The outdated server will be replaced by a state-of-the-art machine soon. We will present improvements of the Oracle configuration, the optimization of SQL statements, and the performance tuning of database design by adding new indexes which proved directly visible in accelerator operation, while data integrity was improved by additional foreign key constraints. (authors)

  1. Three nights leg thermal therapy could improve sleep quality in patients with chronic heart failure.

    Science.gov (United States)

    Sawatari, Hiroyuki; Nishizaka, Mari K; Miyazono, Mami; Ando, Shin-Ichi; Inoue, Shujiro; Takemoto, Masao; Sakamoto, Takafumi; Goto, Daisuke; Furumoto, Tomoo; Kinugawa, Shintaro; Hashiguchi, Nobuko; Rahmawati, Anita; Chishaki, Hiroaki; Ohkusa, Tomoko; Magota, Chie; Tsutsui, Hiroyuki; Chishaki, Akiko

    2018-02-01

    Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep (p quality (p improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients.

  2. Personality differences among patients with chronic aphasia predict improvement in speech-language therapy.

    Science.gov (United States)

    Votruba, Kristen L; Rapport, Lisa J; Whitman, R Douglas; Johnson, Alex; Langenecker, Scott

    2013-01-01

    Negative affectivity and neurocognitive deficits including executive dysfunction have been shown to be detrimental to rehabilitation therapies. However, research on the relationship between neuropsychological deficits and improvement in speech-language therapy (SLT) for aphasia is sparse. To examine the relationships among neurocognitive and psychological functioning and improvement in SLT following aphasia due to stroke. Fifty patients who were ≥ 9 months post stroke and enrolled in outpatient SLT to treat aphasia participated. Using standard language assessment measures, the authors evaluated language functioning at initiation of the study and after participants completed various SLT protocols. Executive functioning, visuospatial skills, attention, and memory also were assessed to provide indices of convergent and discriminant validity. Participants' mood and affectivity were evaluated by self-report, and their functional abilities and recovery of function since stroke were assessed via caregiver report. A multiple regression model testing the combined powers of neurocognitive and psychological variables was significant (P = .004, R2 = 0.33), with psychological and neurocognitive functioning accounting for 15% of the variance in relative language change beyond that accounted for by stroke severity and gross cognitive functioning. Negative affectivity expressed on the Positive and Negative Affectivity Scale made unique contributions to the model. Improvement in SLT is substantially related to neurocognitive and psychological functioning, particularly affectivity. Assessment of these characteristics may assist in identifying patients who are likely to improve and in tailoring treatment programs to yield optimal outcomes.

  3. School-based Telerehabilitation In Occupational Therapy: Using Telerehabilitation Technologies to Promote Improvements in Student Performance

    Directory of Open Access Journals (Sweden)

    Melanie Joy Criss

    2013-06-01

    Full Text Available This article discusses the use of telerehabilitation technologies in occupational therapy for school-based practice. Telerehabilitation, for the purpose of this program, included the implementation of occupational therapy services via two-way interactive videoconferencing technology. The subjects included in this pilot program were children, ages 6 to 11 years, who attended an online charter school and had difficulties in the areas of fine motor and/or visual motor skills which impacted success with handwriting. Each participant completed a virtual evaluation and six 30-minute intervention sessions. The Print Tool™ Assessment was used to determine progress pre- and post-program. A learning coach/student satisfaction survey was given at the end of the program to determine participant satisfaction. Outcomes revealed improvements in handwriting performance for most students who participated in the program and high satisfaction rates reported by all participants.

  4. Sequential (as Opposed to Simultaneous) Antibiotic Therapy Improves Helicobacter pylori Eradication in the Pediatric Population: A Meta-Analysis.

    Science.gov (United States)

    Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

    2016-06-01

    Helicobacter pylori is a common infection associated with many gastrointestinal diseases. Triple or quadruple therapy is the current recommendation for H pylori eradication in children but is associated with success rates as low as 50%. Recent studies have demonstrated that a 10-day sequential therapy regimen, rather than simultaneous antibiotic administration, achieved eradication rates of nearly 95%. This meta-analysis found that sequential therapy increased eradication rates by 14.2% (relative risk [RR] = 1.142; 95% confidence interval [CI] = 1.082-1.207; P sequential therapy significantly improved H pylori eradication rates compared to the 7-day standard therapy (RR = 1.182; 95% CI = 1.102-1.269; p sequential therapy is associated with increased H pylori eradication rates in children compared to standard therapy of equal or shorter duration. © The Author(s) 2015.

  5. INTEGRATION BETWEEN MRI AND PHYSICAL THERAPY TO IMPROVE TREATMENT OF PATIENTS WITH SHOULDER PAIN

    Directory of Open Access Journals (Sweden)

    Awad Mohamed Elkhadir

    2016-08-01

    Full Text Available Background: Shoulder pain is the second most common musculoskeletal disorder treated by physical therapists. The cause for the shoulder pain is multifactorial. However, a specific diagnosis is crucial in the right management of shoulder dysfunction. Therefore, the aim of this study was to find out the efficacy of integrating the MRI for the accurate diagnosis and impact of this on rendering the effective physical therapy interventions in shoulder dysfunction patients. Methods: A retrospective study conducted on 14 patients who undergone an MRI with a 1.5 T unit MAGNETOM Symphony (Siemens, for their shoulder pain, where the diagnosis might be Muscle tears like, subscapularis, infraspinatus,supraspinatus and teres minor muscles; subacromial or subdeltoid bursitis and labral tears were included. All the subjects were then continued with usual physical therapy treatments for four weeks depending on their diagnosis which includes; advice, stretching, mobilization and strengthening exercises, manual therapy, massage, strapping, and electrotherapy . The outcome measures documented from the case sheet were; Visual Analogue Scale grade and passive range of motion of shoulder external / internal rotation and abduction. Results: Paired t test was used to compare the PROM between pre rehabilitation and post rehabilitation testing and the non parametric test, Mann Whitney U test was used for the comparison of VAS. All patients showed a significant improvement in VAS and PROM of abduction, internal and external rotation following physical therapy (P≤ 0.05. Conclusion: MRI is found to be a reliable method of diagnostic procedure for the shoulder pain and the integration of MRI and physical therapy to treat shoulder dysfunction leads to a better outcome.

  6. Home- and Community-Based Occupational Therapy Improves Functioning in Frail Older People: A Systematic Review.

    Science.gov (United States)

    De Coninck, Leen; Bekkering, Geertruida E; Bouckaert, Leen; Declercq, Anja; Graff, Maud J L; Aertgeerts, Bert

    2017-08-01

    The objective is to assess the effectiveness of occupational therapy to improve performance in daily living activities in community-dwelling physically frail older people. We conducted a systematic review and meta-analysis. We included randomized controlled trials reporting on occupational therapy as intervention, or as part of a multidisciplinary approach. This systematic review was carried out in accordance with the Cochrane methods of systematic reviews of interventions. Meta-analyses were performed to pool results across studies using the standardized mean difference. The primary outcome measures were mobility, functioning in daily living activities, and social participation. Secondary outcome measures were fear of falling, cognition, disability, and number of falling persons. Nine studies met the inclusion criteria. Overall, the studies were of reasonable quality with low risk of bias. There was a significant increase in all primary outcomes. The pooled result for functioning in daily living activities was a standardized mean difference of -0.30 (95% CI -0.50 to -0.11; P = .002), for social participation -0.44 (95% CI -0.69, -0.19; P = .0007) and for mobility -0.45 (95% CI -0.78 to -0.12; P = .007). All secondary outcomes showed positive trends, with fear of falling being significant. No adverse effects of occupational therapy were found. There is strong evidence that occupational therapy improves functioning in community-dwelling physically frail older people. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  7. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

    Science.gov (United States)

    Foley, T Raymond; Singh, Gagan D; Kokkinidis, Damianos G; Choy, Ho-Hin K; Pham, Thai; Amsterdam, Ezra A; Rutledge, John C; Waldo, Stephen W; Armstrong, Ehrin J; Laird, John R

    2017-07-15

    The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P =0.14). Demographics including age (68±12 versus 67±10 years, P =0.25), smoking history (76% versus 80%, P =0.42), diabetes mellitus (54% versus 48%, P =0.17), and hypertension (88% versus 89%, P =0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P =0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P =0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P =0.02). In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Quality Improvement of Nasal Continuous Positive Airway Pressure Therapy in Neonatal Intensive Care Unit.

    Science.gov (United States)

    Chen, Chien-Yi; Chou, An-Kuo; Chen, Yu-Lien; Chou, Hung-Chieh; Tsao, Po-Nien; Hsieh, Wu-Shiun

    2017-06-01

    Nasal continuous positive airway pressure (NCPAP) therapy is widely used in neonates, but the clinical practice varies. However, nursing practice differs among individuals, and an inappropriate application method may delay the respiratory therapy, influence the beneficial effect of NCPAP, and increase complications. We introduced a quality improvement project to expedite the application of NCPAP therapy and decrease the incidence of nasal trauma. A new strategy of mobile NCPAP cart with prepacked fixation kits and a written protocol was implemented from April 2006. All medical staff answered a questionnaire to assess their basic knowledge before and after intensive training. The records of the patients who were treated with NCPAP from October 2005 to November 2006 were reviewed. Fifty-nine medical staff were involved in the project, and their mean score for the questionnaire improved from 69.2 points to 98.3 points after training. From October 2005 to November 2006, 113 infants were recruited in total and 82 of them were admitted after the protocol was implemented. The NCPAP cart dramatically shortened the preparation time (from 520 seconds to 72 seconds) and the application time (from 468 seconds to 200 seconds). The use of the nursing protocol significantly decreased the incidence of nasal trauma in the study population (45.2% vs. 19.6%, p = 0.006), but not in infants with a birth weight of < 1000 g. Risk factors for nasal skin trauma included lower gestational age and birth weight, longer duration of NCPAP use, and lack of standardized nursing care. The mobile NCPAP cart with prepacked fixation kits is a practical way of expediting the initiation of NCPAP therapy. The written nursing protocol decreased the incidence of nasal trauma in infants, except for those with an extremely low birth weight. Copyright © 2016. Published by Elsevier B.V.

  9. Patient-derived xenograft models to improve targeted therapy in epithelial ovarian cancer treatment

    Directory of Open Access Journals (Sweden)

    Clare eScott

    2013-12-01

    Full Text Available Despite increasing evidence that precision therapy targeted to the molecular drivers of a cancer has the potential to improve clinical outcomes, high-grade epithelial ovarian cancer patients are currently treated without consideration of molecular phenotype, and predictive biomarkers that could better inform treatment remain unknown. Delivery of precision therapy requires improved integration of laboratory-based models and cutting-edge clinical research, with pre-clinical models predicting patient subsets that will benefit from a particular targeted therapeutic. Patient-derived xenografts (PDX are renewable tumor models engrafted in mice, generated from fresh human tumors without prior in vitro exposure. PDX models allow an invaluable assessment of tumor evolution and adaptive response to therapy.PDX models have been applied to preclinical drug testing and biomarker identification in a number of cancers including ovarian, pancreatic, breast and prostate cancers. These models have been shown to be biologically stable and accurately reflect the patient tumor with regards to histopathology, gene expression, genetic mutations and therapeutic response. However, pre-clinical analyses of molecularly annotated PDX models derived from high-grade serous ovarian cancer (HG-SOC remain limited. In vivo response to conventional and/or targeted therapeutics has only been described for very small numbers of individual HG-SOC PDX in conjunction with sparse molecular annotation and patient outcome data. Recently, two consecutive panels of epithelial ovarian cancer PDX correlate in vivo platinum response with molecular aberrations and source patient clinical outcomes. These studies underpin the value of PDX models to better direct chemotherapy and predict response to targeted therapy. Tumor heterogeneity, before and following treatment, as well as the importance of multiple molecular aberrations per individual tumor underscore some of the important issues

  10. Cognitive-behavioral therapy improves the quality of life of patients with acromegaly.

    Science.gov (United States)

    Kunzler, Lia Silvia; Naves, Luciana Ansaneli; Casulari, Luiz Augusto

    2018-06-01

    The delayed diagnosis, altered body image, and clinical complications associated with acromegaly impair quality of life. To assess the efficacy of the cognitive-behavioral therapy (CBT) technique "Think Healthy" to increase the quality of life of patients with acromegaly. This non-randomized clinical trial examined ten patients with acromegaly (nine women and one man; mean age, 55.5 ± 8.4 years) from a convenience sample who received CBT. The intervention included nine weekly group therapy sessions. The quality of life questionnaire the 36-Item Short Form Survey (SF-36) and the Beck Depression Inventory (BDI) were administered during the pre- and post-intervention phases. The Wilcoxon signed-rank test was performed to assess the occurrence of significant differences. According to the SF-36, the general health domain significantly improved (d'  = - 0.264; p = 0.031). The mental health domain improved considerably (d'  = - 1.123; p = 0.012). Physical functioning showed a non-significant trend toward improvement (d'  = - 0.802; p = 0.078), although four of the five patients who showed floor effects improved and remained at this level. Regarding emotional well-being, five patients showed floor effects and four improved, and the condition did not change among any of the four patients who showed ceiling effects. No significant changes were found with regard to the other domains. No significant differences in the BDI were found before or after the intervention. The technique presented herein effectively improved the quality of life of patients with acromegaly with different levels of disease activity, type, and treatment time.

  11. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  12. Mindfulness based cognitive therapy improves frontal control in bipolar disorder: a pilot EEG study

    Directory of Open Access Journals (Sweden)

    Howells Fleur M

    2012-02-01

    Full Text Available Abstract Background Cognitive processing in Bipolar Disorder is characterized by a number of attentional abnormalities. Mindfulness Based Cognitive Therapy combines mindfulness meditation, a form of attentional training, along with aspects of cognitive therapy, and may improve attentional dysfunction in bipolar disorder patients. Methods 12 euthymic BD patients and 9 control participants underwent record of electroencephalography (EEG, band frequency analysis during resting states (eyes open, eyes closed and during the completion of a continuous performance task (A-X version, EEG event-related potential (ERP wave component analysis. The individuals with BD completed an 8-week MBCT intervention and record of EEG was repeated. Results (1 Brain activity, individuals with BD showed significantly decreased theta band power, increased beta band power, and decreased theta/beta ratios during the resting state, eyes closed, for frontal and cingulate cortices. Post MBCT intervention improvement over the right frontal cortex was seen in the individuals with BD, as beta band power decreased. (2 Brain activation, individuals with BD showed a significant P300-like wave form over the frontal cortex during the cue. Post MBCT intervention the P300-like waveform was significantly attenuated over the frontal cortex. Conclusions Individuals with BD show decreased attentional readiness and activation of non-relevant information processing during attentional processes. These data are the first that show, MBCT in BD improved attentional readiness, and attenuated activation of non-relevant information processing during attentional processes.

  13. Chemoradiation therapy of esophageal cancer. Relationship between improvement of dysphagia and treatment outcome

    International Nuclear Information System (INIS)

    Mizutani, Yoshihide; Kitahara Tadashi

    2004-01-01

    The purpose of the study was to determine retrospectively whether the extent of dysphagia influenced the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. 46 patients had dysphagia before treatment, in which 39 patients were treated with a combination of chemotherapy and irradiation. The remaining 7 patients were treated with irradiation alone. Forty six patients were divided into 5 groups according to the dysphagia score standard to obtain a relationship between the extent of dysphagia and the survival rate of the patients after treatment. Thirty out of 46 patients (65.2%) became able to swallow solid food after treatment. In these patients, the median survival period was 12 months and the one-year survival rate was 53.2%. However, dysphagia was not improved in 16 patients and their median survival period was 4 months, the one-year survival rate was 17.9%. The survival rate after treatment was definitely higher in the patients with improvement of dysphagia. Regarding esophageal cancer, the patients with cancer in the upper esophagus had the worse survival rate. Improvement of dysphagia was an important factor to control the survival rate after chemoradiation therapy in patients with advanced esophageal cancer. (author)

  14. Melatonin Therapy Prevents Programmed Hypertension and Nitric Oxide Deficiency in Offspring Exposed to Maternal Caloric Restriction

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2014-01-01

    Full Text Available Nitric oxide (NO deficiency is involved in the development of hypertension, a condition that can originate early in life. We examined whether NO deficiency contributed to programmed hypertension in offspring from mothers with calorie-restricted diets and whether melatonin therapy prevented this process. We examined 3-month-old male rat offspring from four maternal groups: untreated controls, 50% calorie-restricted (CR rats, controls treated with melatonin (0.01% in drinking water, and CR rats treated with melatonin (CR + M. The effect of melatonin on nephrogenesis was analyzed using next-generation sequencing. The CR group developed hypertension associated with elevated plasma asymmetric dimethylarginine (ADMA, a nitric oxide synthase inhibitor, decreased L-arginine, decreased L-arginine-to-ADMA ratio (AAR, and decreased renal NO production. Maternal melatonin treatment prevented these effects. Melatonin prevented CR-induced renin and prorenin receptor expression. Renal angiotensin-converting enzyme 2 protein levels in the M and CR + M groups were also significantly increased by melatonin therapy. Maternal melatonin therapy had long-term epigenetic effects on global gene expression in the kidneys of offspring. Conclusively, we attributed these protective effects of melatonin on CR-induced programmed hypertension to the reduction of plasma ADMA, restoration of plasma AAR, increase of renal NO level, alteration of renin-angiotensin system, and epigenetic changes in numerous genes.

  15. Group play therapy for improving mental coping ability in children with asthma

    Directory of Open Access Journals (Sweden)

    Qian WANG

    2012-08-01

    Full Text Available Objective To explore the role of group play therapy in the improvement of mental coping ability in children with asthma. Methods Forty-four asthmatic children with behavior problems were randomly divided into experimental group (n=25 and control group (n=19. All children received two tests. The tools in this research were Achenbach Child Behavior Checklist (CBCL and Coping with a Disease Questionnaire (CODI. Before intervention, both groups received pretest. Members from the experimental group were provided with counseling for 3 months, once every two weeks for a total of 6 times, while during this period the members of the control group had not any experimental intervention.After intervention, the two groups received posttest. Five patients dropped out, and 39 went through this research (20 in experimental group and 19 in control group. The effects of group play therapy on behavior problems and coping strategy of children with asthma were evaluated. Results There was no statistically significant differences in the general information (age, sex, education, parents' marriage status and family structure and basic score of CBCL and CODI between the two groups (P > 0.05. After intervention, the scores of social problems, social withdrawal, depression, compulsive behavior, aggressive behavior and immature and total behavior problem score dropped significantly in experimental group (P < 0.05 while there were no significant changes in control group. And the scores of acceptance, avoidance and emotional reaction increased significantly in experimental group (P < 0.05 while there were no significant changes in control group. Conclusions Group play therapy can improve the children's confidence and interpersonal adaptability and emotion management capacity, thus correcting deviant behavior, ameliorate coping strategy, improving mental coping capability, and promote the development of mental health in children with asthma.

  16. Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis

    DEFF Research Database (Denmark)

    Nissen, C V; Heerfordt, I M; Wiegell, S R

    2017-01-01

    BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is highly effective for treating actinic keratosis (AK) on the face/scalp, but less effective on the extremities. Insufficient accumulation of protoporphyrin IX (PpIX) may cause these inferior efficacy rates. However...... (P = 0·001 and P = 0·002, respectively). However, the median total clearance rates did not improve accordingly: 3hC+ (55·0%), 21hC- (55·0%) and 21hC+ (53·6%). Conversely, insufficient PpIX accumulation in the 3hC- regimen led to a significantly lower clearance rate (33·3%) than the other regimens (P...

  17. The Relationship between Symptom Relief and Psychosocial Functional Improvement during Acute Electroconvulsive Therapy for Patients with Major Depressive Disorder.

    Science.gov (United States)

    Lin, Ching-Hua; Yang, Wei-Cheng

    2017-07-01

    We aimed to compare the degree of symptom relief to psychosocial functional (abbreviated as "functional") improvement and explore the relationships between symptom relief and functional improvement during acute electroconvulsive therapy for patients with major depressive disorder. Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy were recruited. Electroconvulsive therapy was generally performed for a maximum of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating Scale, and psychosocial functioning (abbreviated as "functioning"), using the Modified Work and Social Adjustment Scale, were assessed before electroconvulsive therapy, after every 3 electroconvulsive therapy treatments, and after the final electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale scores were converted to T-score units to compare the degrees of changes between depressive symptoms and functioning after electroconvulsive therapy. Structural equation modeling was used to test the relationships between 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale during acute electroconvulsive therapy. One hundred sixteen patients who completed at least the first 3 electroconvulsive therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression Rating Scale T-scores was significantly greater than that of Modified Work and Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model analyzed by structural equation modeling satisfied all indices of goodness-of-fit (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17-item Hamilton Depression Rating Scale change did not predict subsequent Modified Work and Social Adjustment Scale change. Functioning improved less than depressive symptoms during acute electroconvulsive therapy. Symptom reduction did not predict subsequent functional improvement

  18. Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

    LENUS (Irish Health Repository)

    2011-04-01

    Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

  19. Improving efficiency and safety in external beam radiation therapy treatment delivery using a Kaizen approach.

    Science.gov (United States)

    Kapur, Ajay; Adair, Nilda; O'Brien, Mildred; Naparstek, Nikoleta; Cangelosi, Thomas; Zuvic, Petrina; Joseph, Sherin; Meier, Jason; Bloom, Beatrice; Potters, Louis

    Modern external beam radiation therapy treatment delivery processes potentially increase the number of tasks to be performed by therapists and thus opportunities for errors, yet the need to treat a large number of patients daily requires a balanced allocation of time per treatment slot. The goal of this work was to streamline the underlying workflow in such time-interval constrained processes to enhance both execution efficiency and active safety surveillance using a Kaizen approach. A Kaizen project was initiated by mapping the workflow within each treatment slot for 3 Varian TrueBeam linear accelerators. More than 90 steps were identified, and average execution times for each were measured. The time-consuming steps were stratified into a 2 × 2 matrix arranged by potential workflow improvement versus the level of corrective effort required. A work plan was created to launch initiatives with high potential for workflow improvement but modest effort to implement. Time spent on safety surveillance and average durations of treatment slots were used to assess corresponding workflow improvements. Three initiatives were implemented to mitigate unnecessary therapist motion, overprocessing of data, and wait time for data transfer defects, respectively. A fourth initiative was implemented to make the division of labor by treating therapists as well as peer review more explicit. The average duration of treatment slots reduced by 6.7% in the 9 months following implementation of the initiatives (P = .001). A reduction of 21% in duration of treatment slots was observed on 1 of the machines (P Kaizen approach has the potential to improve operational efficiency and safety with quick turnaround in radiation therapy practice by addressing non-value-adding steps characteristic of individual department workflows. Higher effort opportunities are identified to guide continual downstream quality improvements. Copyright © 2017 American Society for Radiation Oncology. Published by

  20. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  1. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  2. Improving the efficacy and safety of engineered T cell therapy for cancer.

    Science.gov (United States)

    Shi, Huan; Liu, Lin; Wang, Zhehai

    2013-01-28

    Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is a powerful immunotherapeutics approach against metastatic melanoma. The success of TIL therapy has led to novel strategies for redirecting normal T cells to recognize tumor-associated antigens (TAAs) by genetically engineering tumor antigen-specific T cell receptors (TCRs) or chimeric antigen receptor (CAR) genes. In this manner, large numbers of antigen-specific T cells can be rapidly generated compared with the longer term expansion of TILs. Great efforts have been made to improve these approaches. Initial clinical studies have demonstrated that genetically engineered T cells can mediate tumor regression in vivo. In this review, we discuss the development of TCR and CAR gene-engineered T cells and the safety concerns surrounding the use of these T cells in patients. We highlight the importance of judicious selection of TAAs for modified T cell therapy and propose solutions for potential "on-target, off-organ" toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ying, C. K. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu (Malaysia); Kamil, W. A. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and Radiology Department, Hospital USM, Kota Bharu (Malaysia); Shuaib, I. L. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang (Malaysia); Matsufuji, Naruhiro [Research Centre of Charged Particle Therapy, National Institute of Radiological Sciences, NIRS, Chiba (Japan)

    2014-02-12

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations.

  4. A Mirror Therapy-Based Action Observation Protocol to Improve Motor Learning After Stroke.

    Science.gov (United States)

    Harmsen, Wouter J; Bussmann, Johannes B J; Selles, Ruud W; Hurkmans, Henri L P; Ribbers, Gerard M

    2015-07-01

    Mirror therapy is a priming technique to improve motor function of the affected arm after stroke. To investigate whether a mirror therapy-based action observation (AO) protocol contributes to motor learning of the affected arm after stroke. A total of 37 participants in the chronic stage after stroke were randomly allocated to the AO or control observation (CO) group. Participants were instructed to perform an upper-arm reaching task as fast and as fluently as possible. All participants trained the upper-arm reaching task with their affected arm alternated with either AO or CO. Participants in the AO group observed mirrored video tapes of reaching movements performed by their unaffected arm, whereas participants in the CO group observed static photographs of landscapes. The experimental condition effect was investigated by evaluating the primary outcome measure: movement time (in seconds) of the reaching movement, measured by accelerometry. Movement time decreased significantly in both groups: 18.3% in the AO and 9.1% in the CO group. Decrease in movement time was significantly more in the AO compared with the CO group (mean difference = 0.14 s; 95% confidence interval = 0.02, 0.26; P = .026). The present study showed that a mirror therapy-based AO protocol contributes to motor learning after stroke. © The Author(s) 2014.

  5. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    International Nuclear Information System (INIS)

    Ying, C. K.; Kamil, W. A.; Shuaib, I. L.; Matsufuji, Naruhiro

    2014-01-01

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations

  6. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    International Nuclear Information System (INIS)

    Ying, C.K.; Kamil, W.A.; Shuaib, I.L.; Ying, C.K.; Kamil, W.A.

    2013-01-01

    Full-text: Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations. (author)

  7. Does an individual estimation of halflife improve the results of radioiodine therapy of Graves' disease?

    International Nuclear Information System (INIS)

    Schneider, P.; Koerber, C.; Koerber-Hafner, N.; Haenscheid, H.; Reiners, Chr.

    2002-01-01

    Aim: The impact of our dosimetry concept on radioiodine therapy success in Graves' disease (GD) was analysed. Three questions arised: Did individual estimation of pretherapeutic halflife improve therapeutic success? Did individual dosimetry result in accurate dose calculation? Did antithyroid medication have a measurable influence on therapeutic success under the prevailing conditions? Methods: 126 consecutive patients were treated with 200 Gy I-131 in our therapy ward for GD and followed-up six to nine months after therapy. Success quote was assessed using a standardized protocol and treatment was classified as successful when the patients was eu- or hypothyroid, or unsuccessful when he or she presented with a suppressed TSH-level or in hyperthyroid condition after antithyroid medication withdrawal. Antithyroid medication, activity I-131, dose, concentration of fT 3 and fT 4 , specific delivered dose and halflife were put into a multiple regression model to assess their influence on therapeutic success. In order to assess possible factors disturbing the therapeutic outcome, relevant parameters were analyzed using Logit transformation. Results: Out of 126 patients 84 were classified as successfully treated and 42 (33,3%) as failures. A significant influence on the outcome only was found for thyroid mass. However, therapeutic success appeared to be more distinctly determined by the specific delivered dose using an estimated halflife of 5.5 days (Odds: 10.0, p [de

  8. Using negative pressure therapy for improving skin graft taking on genital area defects following Fournier gangrene.

    Science.gov (United States)

    Orhan, Erkan; Şenen, Dilek

    2017-09-01

    Fournier's gangrene is an infective necrotizing fasciitis of the perineal, genital and perianal regions. Treatment includes aggressive surgical debridement that often results in extensive loss of genital skin. Skin grafts may be used for reconstruction but skin grafting of the male genitalia is diffucult because the penis and scrotum are mobile and deformable. A variety of methods are used to secure skin graft to recipient beds. We used negative pressure therapy (NPT) to secure skin grafts and improve skin graft taking. We used negative pressure therapy for graft fixation in 13 male patients who underwent debridements with the indication of Fournier gangrene, and whose defects formed were reconstructed with grafts between January 2009, and January 2014. Information about age of the patients, sessions of negative pressure therapy applied before, and after reconstruction, duration of hospital stay, and graft losses during postoperative period were recorded. Median age of the patients was 56.15 (46-72) years. NPT was applied to patients for an average of 6.64 sessions (4-12) before and 1 sessions after graft reconstruction. Patients were hospitalized for an average of 26.7 (20-39) days. Any graft loss was not seen after NPT. Because of the peculiar anatomy of the genital region, anchoring of grafts is difficult so graft losses are often encountered. Use of NPT for ensuring graft fixation on the genital region prevents skin graft shearing.

  9. Dance/movement therapy for improving psychological and physical outcomes in cancer patients.

    Science.gov (United States)

    Bradt, Joke; Shim, Minjung; Goodill, Sherry W

    2015-01-07

    Current cancer care increasingly incorporates psychosocial interventions. Cancer patients use dance/movement therapy to learn to accept and reconnect with their bodies, build new self-confidence, enhance self-expression, address feelings of isolation, depression, anger and fear and to strengthen personal resources. To update the previously published review that examined the effects of dance/movement therapy and standard care versus standard care alone or standard care and other interventions on psychological and physical outcomes in patients with cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 6), MEDLINE (OvidSP, 1950 to June week 4, 2014), EMBASE (OvidSP, 1980 to 2014 week 26), CINAHL (EBSCOhost, 1982 to July 15 2014), PsycINFO (EBSCOhost, 1806 to July 15 2014), LILACS (Virual Health Library, 1982 to July 15 2014), Science Citation Index (ISI, 1974 to July 15 2014), CancerLit (1983 to 2003), International Bibliography of Theatre and Dance (1989 to July 15 2014), the National Research Register (2000 to September 2007), Proquest Digital Dissertations, ClinicalTrials.gov, and Current Controlled Trials (all to July 15 2014). We handsearched dance/movement therapy and related topics journals, reviewed reference lists and contacted experts. There was no language restriction. We included all randomized and quasi-randomized controlled trials of dance/movement therapy interventions for improving psychological and physical outcomes in patients with cancer. We considered studies only if dance/movement therapy was provided by a formally trained dance/movement therapist or by trainees in a formal dance/movement therapy program. Two review authors independently extracted the data and assessed the methodological quality, seeking additional information from the trial researchers when necessary. Results were presented using standardized mean differences. We identified one new trial for inclusion in this update. In

  10. Improvement in patient–reported outcomes after group poetry therapy of women with breast cancer

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    Mohammad Ali Gozashti

    2017-07-01

    Full Text Available Background: One of the best ways of achieving the patients’ views and expectations about the effects of a therapeutic or palliative intervention on their quality of life is using PatientReported Outcome Measures (PROMs. Poetry therapy as a psychotherapy intervention has been used for palliation of stressful conditions of several chronic diseases and disabilities. In the present study, we aimed to evaluate the effectiveness of group poetry therapy on the quality of life measures in women with breast cancer.Methods: A total of 30 women with breast cancer, undergoing chemotherapy at a referral center in the north of Iran, participated in the current quasi-experimental before-after study conducted in 2016. The study protocol included eight weekly sessions of group poetry therapy using poems from the great Persian poets. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30 was completed by the patients before beginning group poetry therapy and, twice more, one week and two months after the last session. Items of the questionnaire were manually scored and then analyzed using appropriate statistical tests in IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.Results: A total of 28 patients participated in all the group poetry therapy sessions and completed the questionnaire. The mean and standard deviation of age were 45±66. The changes in the score of quality of life from 51.8 to 65.5 and 69 were observed to be significant in the one-week and two-month follow ups (both with P=0.002. Also, changes in symptom score from 34.5 to 23.7 (P=0.01 and functional score from 65.6 to 77.2 (P=0.01 in the two-month follow up were found to be statistically significant.Conclusion: Based on the findings of the study, it can be concluded that group poetry therapy, as a psychotherapy approach, can be used to improve quality of life in breast cancer patients.

  11. IS MANUAL THERAPY A RATIONAL APPROACH TO IMPROVING HEALTH-RELATED QUALITY OF LIFE IN PEOPLE WITH ARTHRITIS?

    Science.gov (United States)

    Cameron, Melainie

    2002-01-01

    Background: People with arthritic disease are advised to participate in gentle exercise on a regular basis, and pursue long-term medication regimes. Alternative therapies are also used by people with arthritis, and may sometimes be recommended by rheumatologists and other medical personnel. Alternative therapies may be divided into two types: active therapies, in which the patient takes a driving role, and passive therapies, in which the therapy cannot proceed unless driven by a therapist. Objective: To review the effectiveness of manual therapy in improving the health-related quality of life (HRQOL) of people with two common arthritis conditions: Osteoarthritis and rheumatoid arthritis. Discussion: Massage, and other passive (practitioner-driven) manual therapies, have been anecdotally reported to improve health-related quality of life (HRQOL) in people with arthritis. Many manual therapists consult with patients who have arthritic diseases, receive referrals from rheumatologists, and consider the arthritic diseases to be within their field of practise. Although there is empirical evidence that manual therapy with some types of arthritis is beneficial, the level of effectiveness however is under-researched. Medical authorities are reluctant to endorse manual therapies for arthritis due to a lack of scientific evidence demonstrating efficacy, safety, and cost effectiveness. PMID:17987169

  12. Neurologic music therapy improves executive function and emotional adjustment in traumatic brain injury rehabilitation.

    Science.gov (United States)

    Thaut, Michael H; Gardiner, James C; Holmberg, Dawn; Horwitz, Javan; Kent, Luanne; Andrews, Garrett; Donelan, Beth; McIntosh, Gerald R

    2009-07-01

    This study examined the immediate effects of neurologic music therapy (NMT) on cognitive functioning and emotional adjustment with brain-injured persons. Four treatment sessions were held, during which participants were given a pre-test, participated in 30 min of NMT that focused on one aspect of rehabilitation (attention, memory, executive function, or emotional adjustment), which was followed by post-testing. Control participants engaged in a pre-test, 30 min of rest, and then a post-test. Treatment participants showed improvement in executive function and overall emotional adjustment, and lessening of depression, sensation seeking, and anxiety. Control participants improved in emotional adjustment and lessening of hostility, but showed decreases in measures of memory, positive affect, and sensation seeking.

  13. Improvement of post-hypoxic action myoclonus with levetiracetam add-on therapy: A case report

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    Božić Ksenija

    2014-01-01

    Full Text Available Introduction. Chronic post-anoxic myoclonus, also known as Lance-Adams syndrome, may develop following hypoxic brain injury, and is resistant to pharmacological therapy. Case report. The patient we presented developed post-anoxic action myoclonus with severe, completely incapacitating myoclonic jerks. Myoclonus did not respond to the treatment with commonly used agents, i.e. valproate and clonazepam alone or in combination. Improvement of the action myoclonus was observed only after adding levetiracetam. Conclusion. Although Lance-Adams syndrome may not be fully curable at this point, levetiracetam appears to be a promising agent that can significantly improve functional level and overall quality of life of patients with this disorder.

  14. Amrubicin therapy improves patients with refractory small-cell lung cancer: A single-arm confirmatory Chinese clinical study

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    Mengli Zheng

    2016-09-01

    Full Text Available Our objective was to evaluate an open-label, multicenter, single-arm study to appraise whether amrubicin therapy improves patients with refractory small-cell lung cancer in Chinese clinical study. Patients (n=95 with refractory small-cell lung cancer received 3 consecutive days amrubicin therapy for 21 days. Overall response rate of response to amrubicin was 39%. Anemia, febrile neutropenia, thrombocytopenia, hyperglycemia, hyponatremia, infection, elevated serum transaminases levels were appeared, but the incidences of adverse events were very few. Our results suggest amrubicin therapy can improve patients with refractory small-cell lung cancer and may be an effective and safe treatment option.

  15. Active music therapy improves cognition and behaviour in chronic vascular encephalopathy: a case report.

    Science.gov (United States)

    Giovagnoli, Anna Rita; Oliveri, Serena; Schifano, Letizia; Raglio, Alfredo

    2014-02-01

    This study describes the effects of active music therapy (AMT) on cognition and behaviour in chronic vascular encephalopathy. A single case study investigated different cognitive and psycho-behavioural changes after AMT. An adult patient with memory, attention, and verbal fluency deficits associated with Vascular Cognitive Impairment-No Dementia (VCI-ND) was treated. A four-months AMT course was based on creative and interactive music playing. Sixteen sessions were conducted simultaneously to the pharmacological therapy. Cognitive performances, mood, interpersonal interactions, and perceived abilities were assessed using standardized neuropsychological and psycho-behavioural measurements. At baseline, the patient reported a tendency to feel tense, nervous, and angry and difficulties in memory and visuospatial performances, frequently accompanied by attention drops. The social network was a habitual component of the patient's life, but not a source of sharing of personal experiences, safety or comfort. Neuropsychological tests showed deficits in object and figure naming, verbal fluency, short and long-term verbal memory, short-term spatial memory, selective attention, and visuomotor coordination. After AMT, the cognitive profile significantly improved in attention, visuomotor coordination, and verbal and spatial memory. Such positive changes were confirmed at the three-months follow-up. An increase of the interpersonal interactions and consistent reduction of anxiety were also observed. In selected patients with VCI-ND, a well-structured AMT intervention added to standard therapy may contribute in determining a stable improvement of cognitive and psycho-behavioural aspects. Controlled studies are needed to confirm these promising results. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

    Science.gov (United States)

    Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

    2017-09-26

    Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile

  17. Superior Mesenteric Artery Syndrome Improved by Enteral Nutritional Therapy according to the Controlling Nutritional Status Score.

    Science.gov (United States)

    Takehara, Kazuhiro; Sakamoto, Kazuhiro; Takahashi, Rina; Kawai, Masaya; Kawano, Shingo; Munakata, Shinya; Sugimoto, Kiichi; Takahashi, Makoto; Kojima, Yutaka; Fukunaga, Tetsu; Kajiyama, Yoshiaki; Kawasaki, Seiji

    2017-01-01

    Superior mesenteric artery syndrome (SMAS) is a relatively rare disease that involves bowel obstruction symptoms, such as vomiting and gastric distension, owing to the compression of the third portion of the duodenum from the front by the superior mesenteric artery (SMA) and from the rear by the abdominal aorta and the spine. SMAS is diagnosed on the basis of an upper gastrointestinal examination series indicating the obstruction of the third portion of the duodenum or a computed tomography scan indicating the narrowing of the branch angle between the aorta and the SMA (i.e., the aorta-SMA angle). Here, we report the case of a 78-year-old woman diagnosed with SMAS after a laparoscopic right hemicolectomy for cecal cancer, whose condition was improved by enteral nutritional therapy. We used her controlling nutritional status (CONUT) score as a nutrition assessment and noted the changes in the aorta-SMA angle over the course of the disease. This patient appeared to develop SMAS, on the basis of a worsened CONUT score and a decreased aorta-SMA angle, owing to the inflammation resulting from the intraoperative dissection of the tissues around the SMA and prolonged postoperative fasting. After the initiation of enteral nutritional therapy, the patient exhibited body weight gain and an improved aorta-SMA angle and CONUT score. Hence, assessment of the aorta-SMA angle and CONUT score is an important preoperative consideration.

  18. Superior Mesenteric Artery Syndrome Improved by Enteral Nutritional Therapy according to the Controlling Nutritional Status Score

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    Kazuhiro Takehara

    2017-11-01

    Full Text Available Superior mesenteric artery syndrome (SMAS is a relatively rare disease that involves bowel obstruction symptoms, such as vomiting and gastric distension, owing to the compression of the third portion of the duodenum from the front by the superior mesenteric artery (SMA and from the rear by the abdominal aorta and the spine. SMAS is diagnosed on the basis of an upper gastrointestinal examination series indicating the obstruction of the third portion of the duodenum or a computed tomography scan indicating the narrowing of the branch angle between the aorta and the SMA (i.e., the aorta-SMA angle. Here, we report the case of a 78-year-old woman diagnosed with SMAS after a laparoscopic right hemicolectomy for cecal cancer, whose condition was improved by enteral nutritional therapy. We used her controlling nutritional status (CONUT score as a nutrition assessment and noted the changes in the aorta-SMA angle over the course of the disease. This patient appeared to develop SMAS, on the basis of a worsened CONUT score and a decreased aorta-SMA angle, owing to the inflammation resulting from the intraoperative dissection of the tissues around the SMA and prolonged postoperative fasting. After the initiation of enteral nutritional therapy, the patient exhibited body weight gain and an improved aorta-SMA angle and CONUT score. Hence, assessment of the aorta-SMA angle and CONUT score is an important preoperative consideration.

  19. Improvement in verbal memory performance in depressed in-patients after treatment with electroconvulsive therapy.

    Science.gov (United States)

    Biedermann, S V; Bumb, J M; Demirakca, T; Ende, G; Sartorius, A

    2016-12-01

    Electroconvulsive therapy (ECT) is a highly effective and well-tolerated therapy for severe and treatment-resistant depression. Cognitive side-effects are still feared by some patients and clinicians. Importantly, cognitive impairments are among the most disabling symptoms of depression itself. Patients suffering from a severe episode of depression were treated with either ECT or treatment as usual (TAU) in an in-patient setting. Matched healthy participants served as controls (HC). Verbal memory was tested with the California Verbal Learning Test (CVLT) before the specific treatment started (ECT = 15, TAU = 16, HC = 31) and 2 months after the last ECT session or 2 months after discharge respectively. Before the specific treatment started, depressed patients performed substantially worse compared with HC in total, short- and long-delay recall in the CVLT, while the ECT group showed the worst performance. More severely depressed patients showed worse performances in these measures. Intriguingly, verbal memory showed a significant improvement in ECT-treated patients, but not in the other groups. No differences between the groups were found at follow-up. Contrary to the widely feared assumption that ECT has long-term impact on memory functions, we found evidence that ECT is superior to TAU in improving verbal memory in depressed patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Myosin7a deficiency results in reduced retinal activity which is improved by gene therapy.

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    Pasqualina Colella

    Full Text Available Mutations in MYO7A cause autosomal recessive Usher syndrome type IB (USH1B, one of the most frequent conditions that combine severe congenital hearing impairment and retinitis pigmentosa. A promising therapeutic strategy for retinitis pigmentosa is gene therapy, however its pre-clinical development is limited by the mild retinal phenotype of the shaker1 (sh1(-/- murine model of USH1B which lacks both retinal functional abnormalities and degeneration. Here we report a significant, early-onset delay of sh1(-/- photoreceptor ability to recover from light desensitization as well as a progressive reduction of both b-wave electroretinogram amplitude and light sensitivity, in the absence of significant loss of photoreceptors up to 12 months of age. We additionally show that subretinal delivery to the sh1(-/- retina of AAV vectors encoding the large MYO7A protein results in significant improvement of sh1(-/- photoreceptor and retinal pigment epithelium ultrastructural anomalies which is associated with improvement of recovery from light desensitization. These findings provide new tools to evaluate the efficacy of experimental therapies for USH1B. In addition, although AAV vectors expressing large genes might have limited clinical applications due to their genome heterogeneity, our data show that AAV-mediated MYO7A gene transfer to the sh1(-/- retina is effective.

  1. Solid Dispersion of Curcumin as Polymeric Films for Bioenhancement and Improved Therapy of Rheumatoid Arthritis.

    Science.gov (United States)

    Mande, Prashant P; Bachhav, Sagar S; Devarajan, Padma V

    2016-08-01

    The aim of our study was development of advanced third generation Curcumin self microemulsifying composition solid dispersion (Cur SMEC-SD) with high drug loading, improved stability, rapid in-vitro dissolution and enhanced bioavailability for improved therapy of rheumatoid arthritis. The Cur SMEC-SD comprising polymers (KollidonVA64[KVA], Eudragits, HPMC and Soluplus) and self microemulsifying composition of surfactant:co-surfactant:oil were coated onto rapidly disintegrating inert tablet core. SDs evaluated for stability, in-vitro release and bioenhancement. Cur SMEC-SDs exhibited high Cur loading of 45% w/w and microemulsion formation with globule size (~100 nm) irrespective of polymers. Among the polymers, SD with KVA revealed exceptionally low contact angle (7°C) and rapid in-vitro release (t50%-6.45 min). No crystallization was evident as confirmed by SEM, DSC and XRD and is attributed to SMEC aided solubilization/amorphisation, and interaction of KVA with Cur seen in the FTIR spectra. Stability was confirmed as per ICH guidelines. Remarkable bioenhancement with Cur SMEC-SD was confirmed by the > four fold and a two fold compared to Cur and Cur-SD without SMEC respectively. High efficacy ~ 80% compared to Indomethacin, seen with rheumatoid arthritis (RA) induced rats coupled with no adverse toxicity. The advanced third generation Cur SMEC-SD presents a practical technological advancement and suggests Cur SMEC-SD as promising alternative for RA therapy.

  2. Constraint-induced movement therapy improves upper limb activity and participation in hemiplegic cerebral palsy: a systematic review

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    Hsiu-Ching Chiu

    2016-07-01

    Full Text Available Questions: Does constraint-induced movement therapy improve activity and participation in children with hemiplegic cerebral palsy? Does it improve activity and participation more than the same dose of upper limb therapy without restraint? Is the effect of constraint-induced movement therapy related to the duration of intervention or the age of the children? Design: Systematic review of randomised trials with meta-analysis. Participants: Children with hemiplegic cerebral palsy with any level of motor disability. Intervention: The experimental group received constraint-induced movement therapy (defined as restraint of the less affected upper limb during supervised activity practice of the more affected upper limb. The control group received no intervention, sham intervention, or the same dose of upper limb therapy. Outcome measures: Measures of upper limb activity and participation were used in the analysis. Results: Constraint-induced movement therapy was more effective than no/sham intervention in terms of upper limb activity (SMD 0.63, 95% CI 0.20 to 1.06 and participation (SMD 1.21, 95% CI 0.41 to 2.02. However, constraint-induced movement therapy was no better than the same dose of upper limb therapy without restraint either in terms of upper limb activity (SMD 0.05, 95% CI –0.21 to 0.32 or participation (SMD –0.02, 95% CI –0.34 to 0.31. The effect of constraint-induced movement therapy was not related to the duration of intervention or the age of the children. Conclusions: This review suggests that constraint-induced movement therapy is more effective than no intervention, but no more effective than the same dose of upper limb practice without restraint. Registration: PROSPERO CRD42015024665. [Chiu H-C, Ada L (2016 Constraint-induced movement therapy improves upper limb activity and participation in hemiplegic cerebral palsy: a systematic review. Journal of Physiotherapy 62: 130–137

  3. Nutrition therapy with high intensity interval training to improve prostate cancer-related fatigue in men on androgen deprivation therapy: a study protocol.

    Science.gov (United States)

    Baguley, Brenton J; Skinner, Tina L; Leveritt, Michael D; Wright, Olivia R L

    2017-01-03

    Cancer-related fatigue is one of the most prevalent, prolonged and distressing side effects of prostate cancer treatment with androgen deprivation therapy. Preliminary evidence suggests natural therapies such as nutrition therapy and structured exercise prescription can reduce symptoms of cancer-related fatigue. Men appear to change their habitual dietary patterns after prostate cancer diagnosis, yet prostate-specific dietary guidelines provide limited support for managing adverse side effects of treatment. The exercise literature has shown high intensity interval training can improve various aspects of health that are typically impaired with androgen deprivation therapy; however exercise at this intensity is yet to be conducted in men with prostate cancer. The purpose of this study is to examine the effects of nutrition therapy beyond the current healthy eating guidelines with high intensity interval training for managing cancer-related fatigue in men with prostate cancer treated with androgen deprivation therapy. This is a two-arm randomized control trial of 116 men with prostate cancer and survivors treated with androgen deprivation therapy. Participants will be randomized to either the intervention group i.e. nutrition therapy and high intensity interval training, or usual care. The intervention group will receive 20 weeks of individualized nutrition therapy from an Accredited Practising Dietitian, and high intensity interval training (from weeks 12-20 of the intervention) from an Accredited Exercise Physiologist. The usual care group will maintain their standard treatment regimen over the 20 weeks. Both groups will undertake primary and secondary outcome testing at baseline, week 8, 12, and 20; testing includes questionnaires of fatigue and quality of life, objective measures of body composition, muscular strength, cardiorespiratory fitness, biomarkers for disease progression, as well as dietary analysis. The primary outcomes for this trial are measures of

  4. Clinical study of the improvement of butylphthalide combined with edaravone therapy on neural functional recovery in acute cerebral infarction after interventional therapy

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    Juan-Li Jiang

    2016-08-01

    Full Text Available Objective: To study the improvement value of butylphthalide combined with edaravone therapy on neural functional recovery in acute cerebral infarction after interventional therapy. Methods: Patients with acute cerebral infarction who received interventional therapy in our hospital from May 2012 to May 2015 were randomly divided into antioxidant group and control group, control group received conventional anti-platelet and lipid-lowering therapy, antioxidant group received butylphthalide and edaravone on the basis of conventional treatment, and the levels of serum oxygen free radicals, oxidation products, antioxidants and S100β were determined. Results: 3 d after treatment, serum •OH, •O2, NO• and •ONOO- content of both antioxidant group and control group were lower than those instantly after interventional therapy, and serum •OH, •O2, NO• and •ONOO- content of antioxidant group 3 d after treatment were lower than those of control group; 3 d after treatment, serum MDA and AOPP content of antioxidant group were significantly lower than those of control group while SOD and GSH content were significantly higher than those of control group; 3 d, 5 d and 7 d after treatment, serum S100β levels of both antioxidant group and control group were lower than those instantly after interventional therapy, and serum S100β levels of antioxidant group 3 d, 5 d and 7 d after treatment were lower than those of control group. Conclusion: Butylphthalide combined with edaravone therapy for acute cerebral infarction after interventional therapy can improve neural functional recovery, and the functioning molecular target of the treatment is to remove oxygen free radicals.

  5. An educational cartoon accelerates amblyopia therapy and improves compliance, especially among children of immigrants.

    Science.gov (United States)

    Tjiam, Angela M; Holtslag, Gerdien; Vukovic, Elizabet; Asjes-Tydeman, Wijnanda L; Loudon, Sjoukje E; Borsboom, Gerard J J M; de Koning, Harry J; Simonsz, Huibert J

    2012-11-01

    We showed previously that an educational cartoon that explains without words why amblyopic children should wear their eye patch improves compliance, especially in children of immigrant parents who speak Dutch poorly. We now implemented this cartoon in clinics in low socioeconomic status (SES) areas with a large proportion of immigrants and clinics elsewhere in the Netherlands. Clinical, prospective, nonrandomized, preimplementation, and postimplementation study. Amblyopic children aged 3 to 6 years who started occlusion therapy. Preimplementation, children received standard orthoptic care. Postimplementation, children starting occlusion therapy received the cartoon in addition. At implementation, treating orthoptists followed a course on compliance. In low SES areas, compliance was measured electronically during 1 week. The clinical effects of the cartoon-electronically measured compliance, outpatient attendance rate, and speed of reduction in interocular-acuity difference (SRIAD)-averaged over 15 months of observation. In low SES areas, 114 children were included preimplementation versus 65 children postimplementation; elsewhere in the Netherlands, 335 versus 249 children were included. In low SES areas, mean electronically measured compliance was 52.0% preimplementation versus 62.3% postimplementation (P=0.146); 41.8% versus 21.6% (P=0.043) of children occluded less than 30% of prescribed occlusion time. Attendance rates in low SES areas were 60.3% preimplementation versus 76.0% postimplementation (P=0.141), and 82.7% versus 84.5%, respectively, elsewhere in the Netherlands. In low SES areas, the SRIAD was 0.215 log/year preimplementation versus 0.316 log/year postimplementation (P=0.025), whereas elsewhere in the Netherlands, these were 0.244 versus 0.292 log/year, respectively (P=0.005; the SRIAD's improvement was significantly better in low SES areas than elsewhere, P=0.0203). This advantage remained after adjustment for confounding factors. Overall, 25

  6. Trials to optimize dosimetry for 153Sm-EDTMP therapy to improve therapeutic effects

    International Nuclear Information System (INIS)

    Riccabona, G.; Moncayo-Naveda, R.; Oberlandstaetter, M.; Donnemiller, E.; Kendler, D.

    2001-01-01

    In a trial to improve results of therapy with 153 Sm-EDTMP for pain control in patients with disseminated bone metastases dosimetric studies were performed. Out of 30 treated patients 8 were selected for the study at random (5 breast Ca., 3 prostate Ca.). Whole body retention (WBR) of 99m Tc-DPD and 99m Tc-EDTMP was compared with WBR of 153 Sm-EDTMP. Volume of metastases and regional 99 m Tc-phosphonate uptake were assessed by SPECT and conjugated whole body scan data after phantom studies. Effective half-life was estimated also. Clinically results of pain control, side effects and changes of in vitro parameters were followed after therapy for up to 8 months. Therapy was performed in these patients with 55,5 MBq/kg body weight. Results showed an identical pattern of radioactivity distribution on 99 Tc-phosphonate and 153 Sm-EDTMP posttherapy scans, WBR of tracers and therapeutic agent was similar. Tumour volumes were 151-652 mL, count ratios metastases/normal bone 1,72-2,41, so that 6-50% of applied 153 Sm-EDTMP were concentrated in bone lesions. This gave dose estimates of 2,8-13,7 Gy in metastases. Evaluation of clinical results showed that the majority of very good results were observed in patients receiving > 10 Gy (n=3) while with lower doses only 1/4 responded very well. 1 patient was lost to follow-up due to death in the first month after therapy. Moderate and transient myelodepression (platelets) was seen in 3/7 patients without relation to Gy applied. As obviously 153 Sm concentration is not homogenous in bone metastases it can be assumed, that in border zones between tumour and bone 30-40 Gy can be delivered when 10 Gy are calculated for the whole lesion, which would explain the satisfactory therapeutic effect in our study. The dosimetric approach to 153 Sm-EDTMP therapy could necessitate the application of higher amounts of 153 Sm-EDTMP to reach adequate radiation doses in lesions without necessarily increasing risk of myelodepression and with even

  7. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Baume, Dominique; Lilly, Carrie

    2015-01-01

    . Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches

  8. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    had died. Published studies of melanoma therapies were tabled for comparison. Conclusion: The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself. Even with recent therapies, the factors for improved survival remain enigmatic; however, one apparent common denominator in most cases was the persistent use of repeated therapies to reduce tumor bulk, induce tumor necrosis, and/or cause immunostimulation. These cases are instructive, suggesting manipulation of an established, endogenous, existing immune response. These observations provide practical evidence that the course for any patient with advanced melanoma at the outset should be considered unpredictable, open to immunomanipulation, and thus not uniformly fatal. The findings were compared and interpreted with reported newer immunotherapeutic approaches. Keywords: advanced melanoma, clinical responses, immunotherapy, prolonged survival

  9. Antifibrotic Therapy in Simian Immunodeficiency Virus Infection Preserves CD4+ T-Cell Populations and Improves Immune Reconstitution With Antiretroviral Therapy

    Science.gov (United States)

    Estes, Jacob D.; Reilly, Cavan; Trubey, Charles M.; Fletcher, Courtney V.; Cory, Theodore J.; Piatak, Michael; Russ, Samuel; Anderson, Jodi; Reimann, Thomas G.; Star, Robert; Smith, Anthony; Tracy, Russell P.; Berglund, Anna; Schmidt, Thomas; Coalter, Vicky; Chertova, Elena; Smedley, Jeremy; Haase, Ashley T.; Lifson, Jeffrey D.; Schacker, Timothy W.

    2015-01-01

    Even with prolonged antiretroviral therapy (ART), many human immunodeficiency virus-infected individuals have <500 CD4+ T cells/µL, and CD4+ T cells in lymphoid tissues remain severely depleted, due in part to fibrosis of the paracortical T-cell zone (TZ) that impairs homeostatic mechanisms required for T-cell survival. We therefore used antifibrotic therapy in simian immunodeficiency virus-infected rhesus macaques to determine whether decreased TZ fibrosis would improve reconstitution of peripheral and lymphoid CD4+ T cells. Treatment with the antifibrotic drug pirfenidone preserved TZ architecture and was associated with significantly larger populations of CD4+ T cells in peripheral blood and lymphoid tissues. Combining pirfenidone with an ART regimen was associated with greater preservation of CD4+ T cells than ART alone and was also associated with higher pirfenidone concentrations. These data support a potential role for antifibrotic drug treatment as adjunctive therapy with ART to improve immune reconstitution. PMID:25246534

  10. Improvement of therapy for escherichiosis in children infected with Epstein-Barr virus

    Directory of Open Access Journals (Sweden)

    Ye.S. Olkhovskyy

    2017-03-01

    Full Text Available Background. Escherichiosis remains one of the most common intestinal infections, especially among young children. Indigestion of essential nutrients, transient fermentopathy, imbalance of the symbiotic flora, which develop in escherichiosis in combination with general intoxication and water-electrolyte disturbances, can lead to unfavorable outcomes. One of the factors influencing the course of escherichiosis can be Epstein-Barr virus (EBV infection in the child. Purpose of the research — improvement of treatment of children with escherichiosis and EBV infection in different periods of the disease. Materials and methods. We examined 74 children aged 2–3 years, who were treated at the Regional Children’s Clinical Infectious Diseases Hospital in Kharkiv with a diagnosis of moderate-to-severe escherichiosis. A group of 36 children was selected, who received conventional therapy with early gradual restoration of nutrition according to the existing protocol, and the restoration of the qualitative and quantitative composition of food was carried out as soon as possible (first group. The second group was represented by 38 children, who received two-day prolonged gradual restoration of the diet: more gradual increasing the volume of food at each feeding and reducing the number of feedings per day. Children of the second group received drugs containing Lactobacillus, milk thistle extract and B vitamins (once daily with meals from the first day. Ultrasound examination of the abdominal cavity was performed in all children. Results. Analysis of the main clinical, laboratory and instrumental parameters of patients in both groups during their stay in the hospital and one month after the discharge from the hospital revealed that in children of the second group, in whom rational diet therapy was applied, there was a reduction in the duration of bowel dysfunction, abdominal syndrome, flatulence; the parameters of the coprological test and the echosonoscopy

  11. [Acceptance and commitment therapy (ACT) and improving chess performance in promising young chess-players].

    Science.gov (United States)

    Ruiz, Francisco J; Luciano, Carmen

    2009-08-01

    Acceptance and Commitment Therapy (ACT) is shown to be effective in relatively distant fields from the so-called psychological disorders. One of these areas is sport performance improvement. The aim of the current study is to expand the application of brief ACT protocols to improve chess-players' performance. In a previous study, a brief protocol was applied to international-level adult chess-players that was effective. The current study aims to apply an equivalent brief ACT protocol, but in this case, applied in a group format to promising young chess-players. In addition, this brief protocol is compared to a non-intervention control condition. Results show that the ACT brief protocol improved the performance in 5 out of 7 participants, and that none of the chess-players in the control condition reached the established change criterion. The differences between the conditions in chess performance were statistically significant. The results are discussed, emphasizing the replicated impact of a brief ACT protocol on the improvement of chess-players' performance.

  12. Improving the efficiency of cognitive-behavioural therapy by using formal client feedback.

    Science.gov (United States)

    Janse, Pauline D; De Jong, Kim; Van Dijk, Maarten K; Hutschemaekers, Giel J M; Verbraak, Marc J P M

    2017-09-01

    Feedback from clients on their view of progress and the therapeutic relationship can improve effectiveness and efficiency of psychological treatments in general. However, what the added value is of client feedback specifically within cognitive-behavioural therapy (CBT), is not known. Therefore, the extent to which the outcome of CBT can be improved is investigated by providing feedback from clients to therapists using the Outcome Rating Scale (ORS) and Session Rating Scale (SRS). Outpatients (n = 1006) of a Dutch mental health organization either participated in the "treatment as usual" (TAU) condition, or in Feedback condition of the study. Clients were invited to fill in the ORS and SRS and in the Feedback condition therapists were asked to frequently discuss client feedback. Outcome on the SCL-90 was only improved specifically with mood disorders in the Feedback condition. Also, in the Feedback condition, in terms of process, the total number of required treatment sessions was on average two sessions fewer. Frequently asking feedback from clients using the ORS/SRS does not necessarily result in a better treatment outcome in CBT. However, for an equal treatment outcome significantly fewer sessions are needed within the Feedback condition, thus improving efficiency of CBT.

  13. Tailored cognitive-behavioural therapy and exercise training improves the physical fitness of patients with fibromyalgia.

    Science.gov (United States)

    van Koulil, S; van Lankveld, W; Kraaimaat, F W; van Helmond, T; Vedder, A; van Hoorn, H; Donders, A R T; Wirken, L; Cats, H; van Riel, P L C M; Evers, A W M

    2011-12-01

    Patients with fibromyalgia have diminished levels of physical fitness, which may lead to functional disability and exacerbating complaints. Multidisciplinary treatment comprising cognitive-behavioural therapy (CBT) and exercise training has been shown to be effective in improving physical fitness. However, due to the high drop-out rates and large variability in patients' functioning, it was proposed that a tailored treatment approach might yield more promising treatment outcomes. High-risk fibromyalgia patients were randomly assigned to a waiting list control group (WLC) or a treatment condition (TC), with the treatment consisting of 16 twice-weekly sessions of CBT and exercise training tailored to the patient's cognitive-behavioural pattern. Physical fitness was assessed with two physical tests before and 3 months after treatment and at corresponding intervals in the WLC. Treatment effects were evaluated using linear mixed models. The level of physical fitness had improved significantly in the TC compared with the WLC. Attrition rates were low, effect sizes large and reliable change indices indicated a clinically relevant improvement among the TC. A tailored multidisciplinary treatment approach for fibromyalgia consisting of CBT and exercise training is well tolerated, yields clinically relevant changes, and appears a promising approach to improve patients' physical fitness. ClinicalTrials.gov ID NCT00268606.

  14. Use of a risk assessment method to improve the safety of negative pressure wound therapy.

    Science.gov (United States)

    Lelong, Anne-Sophie; Martelli, Nicolas; Bonan, Brigitte; Prognon, Patrice; Pineau, Judith

    2014-06-01

    To conduct a risk analysis of the negative pressure wound therapy (NPWT) care process and to improve the safety of NPWT, a working group of nurses, hospital pharmacists, physicians and hospital managers performed a risk analysis for the process of NPWT care. The failure modes, effects and criticality analysis (FMECA) method was used for this analysis. Failure modes and their consequences were defined and classified as a function of their criticality to identify priority actions for improvement. By contrast to classical FMECA, the criticality index (CI) of each consequence was calculated by multiplying occurrence, severity and detection scores. We identified 13 failure modes, leading to 20 different consequences. The CI of consequences was initially 712, falling to 357 after corrective measures were implemented. The major improvements proposed included the establishment of 6-monthly training cycles for nurses, physicians and surgeons and the introduction of computerised prescription for NPWT. The FMECA method also made it possible to prioritise actions as a function of the criticality ranking of consequences and was easily understood and used by the working group. This study is, to our knowledge, the first to use the FMECA method to improve the safety of NPWT. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  15. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Yang Haihua; Hu Wei; Wang Wei; Chen Peifang; Ding Weijun; Luo Wei

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  16. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression.

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B; Vittengl, Jeffrey R; Barrett, Marna S; Clark, Lee Anna; Thase, Michael E

    2012-05-01

    The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remains unclear. We analyzed data of adult outpatients (N=523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16-20 sessions protocol (50-60 min each) of individual CT according to the treatment manual by Beck et al. (1979). We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d=.90), but interpersonal style did not change substantively during CT (communion d=.03; agency d=.14). High initial agency scores related negatively to the therapeutic alliance (β=-.12), whereas high initial communion scores related positively to the therapeutic alliance (β=.15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β=.13) and higher symptom levels throughout treatment (β=.10). All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B.; Vittengl, Jeffrey R.; Barrett, Marna S.; Clark, Lee Anna; Thase, Michael E.

    2012-01-01

    Background The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remain unclear. Methods We analyzed data of adult outpatients (N = 523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16–20 sessions protocol (50–60 minutes each) of individual CT according to the treatment manual by Beck et al. (1979). Results We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d = .90), but interpersonal style did not change substantively during CT (communion d = .03; agency d = .14). High initial agency scores related negatively to the therapeutic alliance (β = −.12), whereas high initial communion scores related positively to the therapeutic alliance (β = .15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β = .13) and higher symptom levels throughout treatment (β = .10). Limitations All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. Conclusions This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. PMID:22306232

  18. Evolution of Technology for Continuous Renal Replacement Therapy: Forty Years of Improvement.

    Science.gov (United States)

    Ronco, Claudio

    2018-01-01

    Continuous arteriovenous hemofiltration (CAVH) was proposed in 1977 as an alternative treatment for acute renal failure in patients in whom peritoneal dialysis or hemodialysis was clinically or technically precluded. In the mid-1980s, this technique was extended to infants and children. CAVH presented important advantages in the areas of hemodynamic stability, control of circulating volume, and nutritional support. However, there were serious shortcomings such as the need for arterial cannulation and limited solute clearance. These problems were solved by the introduction of continuous arteriovenous hemodiafiltration and continuous arteriovenous hemodialysis, where uremic control could be achieved by increasing countercurrent dialysate flow rates to 1.5 or 2 L/h as necessary, or by venovenous techniques utilizing a double-lumen central venous catheter for vascular access. Thus, continuous venovenous hemofiltration replaced CAVH because of its improved performance and safety. From the initial adoptive technology, specific machines have been designed to permit safe and reliable performance of the therapy. These new machines have progressively undergone a series of technological steps that have resulted in the evolution of highly sophisticated equipment utilized today. A significant number of advances have taken place since the time continuous renal replacement therapy was initiated. In particular, there have been successful experiments with high-volume hemofiltration and high-permeability hemofiltration. The additional and combined use of sorbent has also been tested successfully. Progress has been made in the technology as well as the understanding of the pathophysiology of acute kidney injury. Today, new biomaterials and new devices are available and new frontiers are on the horizon. Although improvements have been made, a lot remains to be done. Critical care nephrology is expected to further evolve in the near future, especially in the area of information and

  19. Use of peers to improve adherence to antiretroviral therapy: a global network meta-analysis.

    Science.gov (United States)

    Kanters, Steve; Park, Jay Jh; Chan, Keith; Ford, Nathan; Forrest, Jamie; Thorlund, Kristian; Nachega, Jean B; Mills, Edward J

    2016-01-01

    It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization's global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression. We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses. Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials. Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART.

  20. Children with Down Syndrome Improved in Motor Functioning and Muscle Tone Following Massage Therapy

    Science.gov (United States)

    Hernandez-Reif, Maria; Field, Tiffany; Largie, Shay; Mora, Dana; Bornstein, Joan; Waldman, Ronnie

    2006-01-01

    Twenty-one moderate to high functioning young children (mean age, two years) with Down syndrome receiving early intervention (physical therapy, occupational therapy and speech therapy) were randomly assigned to additionally receive two 0.5-hour massage therapy or reading sessions (control group) per week for two months. On the first and last day…

  1. Toward improved target conformity for two spot scanning proton therapy delivery systems using dynamic collimation

    Science.gov (United States)

    Moignier, Alexandra; Gelover, Edgar; Smith, Blake R.; Wang, Dongxu; Flynn, Ryan T.; Kirk, Maura L.; Lin, Liyong; Solberg, Timothy D.; Lin, Alexander; Hyer, Daniel E.

    2016-01-01

    Purpose: To quantify improvement in target conformity in brain and head and neck tumor treatments resulting from the use of a dynamic collimation system (DCS) with two spot scanning proton therapy delivery systems (universal nozzle, UN, and dedicated nozzle, DN) with median spot sizes of 5.2 and 3.2 mm over a range of energies from 100 to 230 MeV. Methods: Uncollimated and collimated plans were calculated with both UN and DN beam models implemented within our in-house treatment planning system for five brain and ten head and neck datasets in patients previously treated with spot scanning proton therapy. The prescription dose and beam angles from the clinical plans were used for both the UN and DN plans. The average reduction of the mean dose to the 10-mm ring surrounding the target between the uncollimated and collimated plans was calculated for the UN and the DN. Target conformity was analyzed using the mean dose to 1-mm thickness rings surrounding the target at increasing distances ranging from 1 to 10 mm. Results: The average reductions of the 10-mm ring mean dose for the UN and DN plans were 13.7% (95% CI: 11.6%–15.7%; p < 0.0001) and 11.5% (95% CI: 9.5%–13.5%; p < 0.0001) across all brain cases and 7.1% (95% CI: 4.4%–9.8%; p < 0.001) and 6.3% (95% CI: 3.7%–9.0%; p < 0.001), respectively, across all head and neck cases. The collimated UN plans were either more conformal (all brain cases and 60% of the head and neck cases) than or equivalent (40% of the head and neck cases) to the uncollimated DN plans. The collimated DN plans offered the highest conformity. Conclusions: The DCS added either to the UN or DN improved the target conformity. The DCS may be of particular interest for sites with UN systems looking for a more economical solution than upgrading the nozzle to improve the target conformity of their spot scanning proton therapy system. PMID:26936726

  2. Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial.

    Science.gov (United States)

    Eeles, Rosalind A; Morden, James P; Gore, Martin; Mansi, Janine; Glees, John; Wenczl, Miklos; Williams, Christopher; Kitchener, Henry; Osborne, Richard; Guthrie, David; Harper, Peter; Bliss, Judith M

    2015-12-10

    To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian cancer. Participants were premenopausal and postmenopausal women who had been diagnosed with epithelial ovarian cancer (any International Federation of Gynecology and Obstetrics stage) 9 or fewer months previously. Ineligible patients included those with deliberately preserved ovarian function, with a history of a hormone-dependent malignancy, or with any contraindications to hormone-replacement therapy. Patients were centrally randomly assigned in a 1:1 ratio to either AHT for 5 years after random assignment or no AHT (control). Main outcome measures were overall survival (OS), defined as time from random assignment to death (any cause), and relapse-free survival, defined as time from random assignment to relapse or death (any cause). Patients who continued, alive and relapse free, were censored at their last known follow-up. A total of 150 patients (n = 75, AHT; n = 75, control) were randomly assigned from 1990 to 1995 from 19 centers in the United Kingdom, Spain, and Hungary; all patients were included in intention-to-treat analyses. The median follow-up in alive patients is currently 19.1 years. Of the 75 patients with AHT, 53 (71%) have died compared with 68 (91%) of 75 patients in the control group. OS was significantly improved in patients who were receiving AHT (hazard ratio, 0.63; 95% CI, 0.44 to 0.90; P = .011). A similar effect was seen for relapse-free survival (hazard ratio, 0.67; 95% CI, 0.47 to 0.97; P = .032). Effects remained after adjustment for known prognostic factors. These results show that women who have severe menopausal symptoms after ovarian cancer treatment can safely take hormone-replacement therapy, and this may, in fact, infer benefits in terms of OS in addition to known advantages in terms of quality of life. © 2015 by American Society of Clinical Oncology.

  3. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    Science.gov (United States)

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Improving Gene Therapy Efficiency through the Enrichment of Human Hematopoietic Stem Cells.

    Science.gov (United States)

    Masiuk, Katelyn E; Brown, Devin; Laborada, Jennifer; Hollis, Roger P; Urbinati, Fabrizia; Kohn, Donald B

    2017-09-06

    Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10 8 to 1 × 10 9 CD34 + cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34 + cells uses LV inefficiently, because the majority of CD34 + cells are short-term progenitors with a limited post-transplant lifespan. Here, we utilized a clinically relevant, immunomagnetic bead (IB)-based method to purify CD34 + CD38 - cells from human bone marrow (BM) and mobilized peripheral blood (mPB). IB purification of CD34 + CD38 - cells enriched severe combined immune deficiency (SCID) repopulating cell (SRC) frequency an additional 12-fold beyond standard CD34 + purification and did not affect gene marking of long-term HSCs. Transplant of purified CD34 + CD38 - cells led to delayed myeloid reconstitution, which could be rescued by the addition of non-transduced CD38 + cells. Importantly, LV modification and transplantation of IB-purified CD34 + CD38 - cells/non-modified CD38 + cells into immune-deficient mice achieved long-term gene-marked engraftment comparable with modification of bulk CD34 + cells, while utilizing ∼7-fold less LV. Thus, we demonstrate a translatable method to improve the clinical and commercial viability of gene therapy for genetic blood cell diseases. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  5. Nutrition Therapy in Critically Ill Patients Following Cardiac Surgery: Defining and Improving Practice.

    Science.gov (United States)

    Rahman, Adam; Agarwala, Ravi; Martin, Claudio; Nagpal, Dave; Teitelbaum, Michael; Heyland, Daren K

    2017-09-01

    Malnutrition is a predictor of poor outcome following cardiac surgery. We define nutrition therapy after cardiac surgery to identify opportunities for improvement. International prospective studies in 2007-2009, 2011, and 2013 were combined. Sites provided institutional and patient characteristics from intensive care unit (ICU) admission to ICU discharge for a maximum of 12 days. Patients had valvular, coronary artery bypass graft (CABG) surgery, or combined procedures and were mechanically ventilated and staying in the ICU for ≥3 days. There were 787 patients from 144 ICUs. In total, 120 patients (15.2%) had valvular surgery, 145 patients (18.4%) had CABG, and 522 patients (66.3%) underwent a combined procedure. Overall, 60.1% of patients received artificial nutrition support. For these patients, 78% received enteral nutrition (EN) alone, 17% received a combination of EN and parenteral nutrition (PN), and 5% received PN alone. The remaining 314 patients (40%) received no nutrition. The mean (SD) time from ICU admission to EN initiation was 2.3 (1.8) days. The adequacy of calories was 32.4% ± 31.9% from EN and PN and 25.5% ± 27.9% for patients receiving only EN. In EN patients, 57% received promotility agents and 20% received small bowel feeding. There was no significant relationship between increased energy or protein provision and 60-day mortality. Postoperative cardiac surgery patients who stay in the ICU for 3 or more days are at high risk for inadequate nutrition therapy. Further studies are required to determine if targeted nutrition therapy may alter clinical outcomes.

  6. A quality improvement project sustainably decreased time to onset of active physical therapy intervention in patients with acute lung injury.

    Science.gov (United States)

    Dinglas, Victor D; Parker, Ann M; Reddy, Dereddi Raja S; Colantuoni, Elizabeth; Zanni, Jennifer M; Turnbull, Alison E; Nelliot, Archana; Ciesla, Nancy; Needham, Dale M

    2014-10-01

    Rehabilitation started early during an intensive care unit (ICU) stay is associated with improved outcomes and is the basis for many quality improvement (QI) projects showing important changes in practice. However, little evidence exists regarding whether such changes are sustainable in real-world practice. To evaluate the sustained effect of a quality improvement project on the timing of initiation of active physical therapy intervention in patients with acute lung injury (ALI). This was a pre-post evaluation using prospectively collected data involving consecutive patients with ALI admitted pre-quality improvement (October 2004-April 2007, n = 120) versus post-quality improvement (July 2009-July 2012, n = 123) from a single medical ICU. The primary outcome was time to first active physical therapy intervention, defined as strengthening, mobility, or cycle ergometry exercises. Among ICU survivors, more patients in the post-quality improvement versus pre-quality improvement group received physical therapy in the ICU (89% vs. 24%, P quality improvement versus pre-quality improvement group, there was a shorter median (interquartile range) time to first physical therapy (4 [2, 6] vs. 11 d [6, 29], P quality improvement period was associated with shorter time to physical therapy (adjusted hazard ratio [95% confidence interval], 8.38 [4.98, 14.11], P quality improvement period. The following variables were independently associated with a longer time to physical therapy: higher Sequential Organ Failure Assessment score (0.93 [0.89, 0.97]), higher FiO2 (0.86 [0.75, 0.99] for each 10% increase), use of an opioid infusion (0.47 [0.25, 0.89]), and deep sedation (0.24 [0.12, 0.46]). In this single-site, pre-post analysis of patients with ALI, an early rehabilitation quality improvement project was independently associated with a substantial decrease in the time to initiation of active physical therapy intervention that was sustained over 5 years. Over the entire pre

  7. Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

    Science.gov (United States)

    Besson, J; Beck, T; Wiesbeck, G; Hämmig, R; Kuntz, A; Abid, S; Stohler, R

    2014-01-01

    Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres. A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. The subset of IMPROVE data

  8. Improvements in muscle symmetry in children with cerebral palsy after equine-assisted therapy (hippotherapy).

    Science.gov (United States)

    Benda, William; McGibbon, Nancy H; Grant, Kathryn L

    2003-12-01

    To evaluate the effect of hippotherapy (physical therapy utilizing the movement of a horse) on muscle activity in children with spastic cerebral palsy. Pretest/post-test control group. Therapeutic Riding of Tucson (TROT), Tucson, AZ. Fifteen (15) children ranging from 4 to 12 years of age diagnosed with spastic cerebral palsy. Children meeting inclusion criteria were randomized to either 8 minutes of hippotherapy or 8 minutes astride a stationary barrel. Remote surface electromyography (EMG) was used to measure muscle activity of the trunk and upper legs during sitting, standing, and walking tasks before and after each intervention. After hippotherapy, significant improvement in symmetry of muscle activity was noted in those muscle groups displaying the highest asymmetry prior to hippotherapy. No significant change was noted after sitting astride a barrel. Eight minutes of hippotherapy, but not stationary sitting astride a barrel, resulted in improved symmetry in muscle activity in children with spastic cerebral palsy. These results suggest that the movement of the horse rather than passive stretching accounts for the measured improvements.

  9. Exercise Therapy Augments the Ischemia-Induced Proangiogenic State and Results in Sustained Improvement after Stroke

    Directory of Open Access Journals (Sweden)

    Man He

    2013-04-01

    Full Text Available The induction of angiogenesis will stimulate endogenous recovery mechanisms, which are involved in the long-term repair and restoration process of the brain after an ischemic event. Here, we tested whether exercise influences the pro-angiogenic factors and outcomes after cerebral infarction in rats. Wistar rats were exposed to two hours of middle-cerebral artery occlusion and reperfusion. Different durations of treadmill training were performed on the rats. The expression of matrix metalloproteinase 2 (MMP2 and vascular endothelial growth factor (VEGF-related genes and proteins were higher over time post-ischemia, and exercise enhanced their expression. Sixteen days post-ischemia, the regional cerebral blood flow in the ischemic striatum was significantly increased in the running group over the sedentary. Although no difference was seen in infarct size between the running and sedentary groups, running evidently improved the neurobehavioral score. The effects of running on MMP2 expression, regional cerebral blood flow and outcome were abolished when animals were treated with bevacizumab (BEV, a VEGF-targeting antibody. Exercise therapy improves long-term stroke outcome by MMP2-VEGF-dependent mechanisms related to improved cerebral blood flow.

  10. Withholding or withdrawing therapy in intensive care units: improving interdisciplinary cooperation

    DEFF Research Database (Denmark)

    Jensen, Hanne Irene; Ammentorp, Jette; Ørding, Helle

    INTRODUCTION. Decisions regarding withholding or withdrawing therapy are common in the intensive care units. The health care professionals involved in the decision-making process do not always assess the situation identically, leading to potential conflicts. Studies have suggested that improving...... (conducted at two hospitals) with participation of primary care physicians, anaesthesiologists (both with and without ICU as their main workplace) and intensive care nurses. A total of 29 participated in the audits. The participants received beforehand three complicated cases (borrowed from other hospitals...... unit conflicts: the conflicus study. Am J Respir Crit Care Med180:853-860. (2) Halvorsen K, Forde R, Nortvedt P (2009) Value choices and considerations when limiting intensive care treatment: a qualitative study. Acta Anaesthesiol Scand 53:10-17 GRANT ACKNOWLEDGMENT. The study was supported...

  11. Football training improves lean body mass in men with prostate cancer undergoing androgen deprivation therapy

    DEFF Research Database (Denmark)

    Uth, J; Hornstrup, Therese; Schmidt, Jakob Friis

    2014-01-01

    Androgen deprivation therapy (ADT) remains a cornerstone in the management of patients with prostate cancer (PCa) despite adverse effects on body composition and functional parameters. We compared the effects of football training with standard care in PCa patients managed with ADT (> 6 months......). Fifty-seven men aged 67 (range: 43-74) were randomly assigned to a football group (FG, n = 29) or a usual care control group (CON, n = 28). The primary outcome was change in lean body mass (LBM) assessed by dual-energy X-ray absorptiometry scanning. Secondary outcomes included changes in knee.......7%; 95%CI 1.3-0.0; P = 0.06), but these changes were not significantly different from CON. In conclusion, football training over 12 weeks improved LBM and muscle strength compared with usual care in men with prostate cancer receiving ADT....

  12. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  13. Traditional Chinese medicine as adjunctive therapy improves the long-term survival of lung cancer patients.

    Science.gov (United States)

    Liao, Yueh-Hsiang; Li, Chia-Ing; Lin, Cheng-Chieh; Lin, Jaung-Geng; Chiang, Jen-Huai; Li, Tsai-Chung

    2017-12-01

    Traditional Chinese medicine is one of the popular alternative treatments for cancer, mainly enhancing host immune response and reducing adverse effect of chemotherapy. This study first explored traditional Chinese medicine treatment effect on long-term survival of lung cancer patients. This study evaluated whether traditional Chinese medicine combined with conventional cancer treatment improved overall survival of lung cancer patients. We had conducted a retrospective cohort study on 111,564 newly diagnosed lung cancer patients in 2000-2009 from National Health Insurance Program database. A total of 23,803 (21.31%) patients used traditional Chinese medicine for lung cancer care. Eligible participants were followed up until 2011 with a mean follow-up period of 1.96 years (standard deviation 2.55) for non-TCM users and 3.04 years (2.85) for traditional Chinese medicine users. Patients with traditional Chinese medicine utilization were significantly more likely to have a 32% decreased risk of death [hazard ratio = 0.62; 95% confidence interval = 0.61-0.63], compared with patients without traditional Chinese medicine utilization after multivariate adjustment. We also observed a similar significant reduction risk across various subgroups of chronic lung diseases. Qing Zao Jiu Fei Tang was the most effective traditional Chinese medicine agent for mortality reduction both in the entire lung cancer (0.81; 0.72-0.91) and matched populations (0.86; 0.78-0.95). This study demonstrated adjunctive therapy with traditional Chinese medicine may improve overall survival of lung cancer patients. This study also suggested traditional Chinese medicine may be used as an adjunctive therapy for cancer treatment. These observational findings need being validated by future randomized controlled trials to rule out the possibility of effect due to holistic care.

  14. Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

    Science.gov (United States)

    Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

    2012-05-01

    A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

  15. 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

  16. 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.

  17. 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) ...

  18. Net improvement of correct answers to therapy questions after pubmed searches: pre/post comparison.

    Science.gov (United States)

    McKibbon, Kathleen Ann; Lokker, Cynthia; Keepanasseril, Arun; Wilczynski, Nancy L; Haynes, R Brian

    2013-11-08

    Clinicians search PubMed for answers to clinical questions although it is time consuming and not always successful. To determine if PubMed used with its Clinical Queries feature to filter results based on study quality would improve search success (more correct answers to clinical questions related to therapy). We invited 528 primary care physicians to participate, 143 (27.1%) consented, and 111 (21.0% of the total and 77.6% of those who consented) completed the study. Participants answered 14 yes/no therapy questions and were given 4 of these (2 originally answered correctly and 2 originally answered incorrectly) to search using either the PubMed main screen or PubMed Clinical Queries narrow therapy filter via a purpose-built system with identical search screens. Participants also picked 3 of the first 20 retrieved citations that best addressed each question. They were then asked to re-answer the original 14 questions. We found no statistically significant differences in the rates of correct or incorrect answers using the PubMed main screen or PubMed Clinical Queries. The rate of correct answers increased from 50.0% to 61.4% (95% CI 55.0%-67.8%) for the PubMed main screen searches and from 50.0% to 59.1% (95% CI 52.6%-65.6%) for Clinical Queries searches. These net absolute increases of 11.4% and 9.1%, respectively, included previously correct answers changing to incorrect at a rate of 9.5% (95% CI 5.6%-13.4%) for PubMed main screen searches and 9.1% (95% CI 5.3%-12.9%) for Clinical Queries searches, combined with increases in the rate of being correct of 20.5% (95% CI 15.2%-25.8%) for PubMed main screen searches and 17.7% (95% CI 12.7%-22.7%) for Clinical Queries searches. PubMed can assist clinicians answering clinical questions with an approximately 10% absolute rate of improvement in correct answers. This small increase includes more correct answers partially offset by a decrease in previously correct answers.

  19. Spiritual Therapy to Improve the Spiritual Well-Being of Iranian Women with Breast Cancer: A Randomized Controlled Trial

    OpenAIRE

    Jafari, Najmeh; Farajzadegan, Ziba; Zamani, Ahmadreza; Bahrami, Fatemeh; Emami, Hamid; Loghmani, Amir; Jafari, Nooshin

    2013-01-01

    Purpose. The aim of this study was to investigate the role of spiritual therapy intervention in improving the spiritual well-being and quality of life (QOL) of Iranian women with breast cancer. Methods. This randomized controlled clinical trial (RCT) recruited 65 women with breast cancer, randomly assigned to a 6-week spirituality-based intervention (n = 34) or control group (n = 31). Before and after six-week spiritual therapy intervention, spiritual well-being and quality of life (QOL) were...

  20. Pilot study: whole body manual subcutaneous adipose tissue (SAT) therapy improved pain and SAT structure in women with lipedema.

    Science.gov (United States)

    Herbst, Karen L; Ussery, Christopher; Eekema, Alyna

    2017-09-20

    Background Lipedema is a common painful subcutaneous adipose tissue (SAT) disorder in women affecting the limbs. SAT therapy is a manual therapy to improve soft tissue quality. Objective Determine if SAT therapy improves pain and structure of lipedema SAT. Design Single arm prospective pilot study. Setting Academic medical center. Patients Seven women, 46 ± 5 years, weight 90 ± 19 kg, with lipedema. Intervention Twelve 90-min SAT therapy sessions over 4 weeks. Outcomes Dual X-ray absorptiometry (DXA) scans, SAT ultrasound (Vevo 2100), leg volumetrics, skin caliper assessment, tissue exam, weight, resting metabolic rate, pain assessment, lower extremity functional scale (LEFS) and body shape questionnaire (BSQ) at baseline and end of study. Results Weight, resting metabolic rate and BSQ did not change significantly. Limb fat over total body fat mass (p = 0.08) and trunk fat over total body mass trended down from baseline (p = 0.08) by DXA. Leg volume and caliper assessments in eight of nine areas (p < 0.007), LEFS (p = 0.002) and average pain (p = 0.007) significantly decreased from baseline. Fibrosis significantly decreased in the nodules, hips and groin. Ultrasound showed improved SAT structure in some subjects. Side effects included pain, bruising, itching, swelling and gastroesophageal reflux disease. All women said they would recommend SAT therapy to other women with lipedema. Limitations Small number of subjects. Conclusion SAT therapy in 4 weeks improved tissue structure, perceived leg function, and volume although shape was not affected. While side effects of SAT therapy were common, all women felt the therapy was beneficial.

  1. Recent trends in robot-assisted therapy environments to improve real-life functional performance after stroke

    OpenAIRE

    Johnson, Michelle J

    2006-01-01

    Abstract Upper and lower limb robotic tools for neuro-rehabilitation are effective in reducing motor impairment but they are limited in their ability to improve real world function. There is a need to improve functional outcomes after robot-assisted therapy. Improvements in the effectiveness of these environments may be achieved by incorporating into their design and control strategies important elements key to inducing motor learning and cerebral plasticity such as mass-practice, feedback, t...

  2. Does manual therapy improve pain and function in patients with plantar fasciitis? A systematic review.

    Science.gov (United States)

    Fraser, John J; Corbett, Revay; Donner, Chris; Hertel, Jay

    2018-05-01

    To assess if manual therapy (MT) in the treatment of plantar fasciitis (PF) patients improves pain and function more effectively than other interventions. A systematic review of all randomized control trials (RCTs) investigating the effects of MT in the treatment of human patients with PF, plantar fasciosis, and heel pain published in English on PubMed, CINAHL, Cochrane, and Web of Science databases was conducted. Research quality was appraised utilizing the PEDro scale. Cohen's d effect sizes (ES) and associated 95% confidence intervals (CI) were calculated between treatment groups. Seven RCTs were selected that employed MT as a primary independent variable and pain and function as dependent variables. Inclusion of MT in treatment yielded greater improvement in function (6 of 7 studies, CI that did not cross zero in 14 of 25 variables, ES = 0.5-21.5) and algometry (3 of 3 studies, CI that did not cross zero in 9 of 10 variables, ES = 0.7-3.0) from 4 weeks to 6 months when compared to interventions such as stretching, strengthening, or modalities. Though pain improved with the inclusion of MT, ES calculations favored MT in only 2 of 6 studies (3 of 13 variables) and was otherwise equivalent in effectiveness to comparison interventions. MT is clearly associated with improved function and may be associated with pain reduction in PF patients. It is recommended that clinicians consider use of both joint and soft tissue mobilization techniques in conjunction with stretching and strengthening when treating patients with PF. Treatment, level 1a.

  3. Low-energy extracorporeal shockwave therapy (ESWT improves metaphyseal fracture healing in an osteoporotic rat model.

    Directory of Open Access Journals (Sweden)

    Gina A Mackert

    Full Text Available As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT, was evaluated as a treatment option for the improvement of osteoporotic fracture healing.A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2 as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR analysis, histomorphometric analysis and biomechanical analysis.The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2 ESWT and with fewer treatment applications per healing period.In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

  4. Occlusion therapy improves phase-alignment of the cortical response in amblyopia.

    Science.gov (United States)

    Kelly, John P; Tarczy-Hornoch, Kristina; Herlihy, Erin; Weiss, Avery H

    2015-09-01

    The visual evoked potential (VEP) generated by the amblyopic visual system demonstrates reduced amplitude, prolonged latency, and increased variation in response timing (phase-misalignment). This study examined VEPs before and after occlusion therapy (OT) and whether phase-misalignment can account for the amblyopic VEP deficits. VEPs were recorded to 0.5-4cycles/degree gratings in 10 amblyopic children (2-6years age) before and after OT. Phase-misalignment was measured by Fourier analysis across a limited bandwidth. Signal-to-noise ratios (SNRs) were estimated from amplitude and phase synchrony in the Fourier domain. Responses were compared to VEPs corrected for phase-misalignment (individual epochs shifted in time to correct for the misalignment). Before OT, amblyopic eyes (AE) had significantly more phase-misalignment, latency prolongation, and lower SNR relative to the fellow eye. Phase-misalignment contributed significantly to low SNR but less so to latency delay in the AE. After OT, phase-alignment improved, SNR improved and latency shortened in the AE. Raw averaged waveforms from the AE improved after OT, primarily at higher spatial frequencies. Correcting for phase-misalignment in the AE sharpened VEP peak responses primarily at low spatial frequencies, but could not account for VEP waveform improvements in the AE after OT at higher spatial frequencies. In summary, VEP abnormalities from the AE are associated with phase-misalignment and reduced SNR possibly related to desynchronization of neuronal activity. The effect of OT on VEP responses is greater than that accounted for by phase-misalignment and SNR alone. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. TO STUDY THE EFFECT OF PLAY THERAPY AND CHILD FRIENDLY CONSTRAINT INDUCED MOMEMENT THERAPY TO IMPROVE HAND FUNCTION IN SPASTIC HEMIPLEGIC CEREBRAL PALSY CHILDREN: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Anjuman Nahar

    2015-12-01

    Full Text Available Background: Cerebral Palsy (CP is a neurodevelopmental disorder caused by nonprogressive lesion in the developing brain. The early central nervous system (CNS damage results in chronic physical disabilities and often includes sensory impairments. In addition CP is often associated with epilepsy and abnormalities of speech, vision, and intellect; it is the selective vulnerability of the brains motor systems that defines the disorder. Child friendly CIMT involves intensive targeted practice with the involved extremity coordination above and beyond their unilateral impairments. Ply Therapy is designed for active involvement of child in performing various tasks. The aim of the study is to evaluate the effectiveness of constraint induced movement therapy and play therapy to improve hand function in spastic hemiplegic cerebral palsy children. Methods: A sample of 30 patients was divided in two groups, each group having 15 children. Convenient sampling was done on the basis of base line assessment and diagnosis of their condition. Duration of the study was 3 months and data collection started at day 0 and at the end of 90 days. Children in group A wore a bivalve plaster cast on the non-involved upper extremity from shoulder to finger tips for the entire time during the session lasting for 2 hours and the plaster cast was removed at the end of the session. B group consists of 15 subjects who received play therapy. The treatment program was conducted individually and adjusted to current needs and abilities of each of the patients. Outcomes: Box and Block test, QOM scale and AOU scale. Results: It was found that there is an improvement in the hand function on application of child friendly CIMT in the patients with spastic hemiplegic cerebral palsy which was found significant using the Mann-Whitney U test (p≤0.005. Conclusion: In this study it has been found that the use of Child friendly CIMT and PLAY THERAPY produces significant improvement in hand

  6. Substrate Deprivation Therapy to Reduce Glycosaminoglycan Synthesis Improves Aspects of Neurological and Skeletal Pathology in MPS I Mice

    Directory of Open Access Journals (Sweden)

    Ainslie L. K. Derrick-Roberts

    2017-02-01

    Full Text Available Mucopolysaccharidosis type I (MPS I is the most common form of the MPS group of genetic diseases. MPS I results from a deficiency in the lysosomal enzyme α-l-iduronidase, leading to accumulation of undegraded heparan and dermatan sulphate glycosaminoglycan (GAG chains in patient cells. MPS children suffer from multiple organ failure and die in their teens to early twenties. In particular, MPS I children also suffer from profound mental retardation and skeletal disease that restricts growth and movement. Neither brain nor skeletal disease is adequately treated by current therapy approaches. To overcome these barriers to effective therapy we have developed and tested a treatment called substrate deprivation therapy (SDT. MPS I knockout mice were treated with weekly intravenous injections of 1 mg/kg rhodamine B for six months to assess the efficacy of SDT. Mice were assessed using biochemistry, micro-CT and a battery of behaviour tests to determine the outcome of treatment. A reduction in female bodyweight gain was observed with the treatment as well as a decrease in lung GAG. Behavioural studies showed slight improvements in inverted grid and significant improvements in learning ability for female MPS I mice treated with rhodamine B. Skeletal disease also improved with a reduction in bone mineral volume observed. Overall, rhodamine B is safe to administer to MPS I knockout mice where it had an effect on improving aspects of neurological and skeletal disease symptoms and may therefore provide a potential therapy or adjunct therapy for MPS I patients.

  7. Mastication movements and sleep quality of patients with myofascial pain: occlusal device therapy improvements.

    Science.gov (United States)

    Vilanova, Larissa Soares Reis; Gonçalves, Thais Marques Simek Vega; Pimentel, Marcele Jardim; Bavia, Paula Furlan; Rodrigues Garcia, Renata Cunha Matheus

    2014-12-01

    Patients with myofascial pain experience impaired mastication, which might also interfere with their sleep quality. The purpose of this study was to evaluate the jaw motion and sleep quality of patients with myofascial pain and the impact of a stabilization device therapy on both parameters. Fifty women diagnosed with myofascial pain by the Research Diagnostic Criteria were enrolled. Pain levels (visual analog scale), jaw movements (kinesiography), and sleep quality (Epworth Sleepiness Scale; Pittsburgh Sleep Quality Index) were evaluated before (control) and after stabilization device use. Range of motion (maximum opening, right and left excursions, and protrusion) and masticatory movements during Optosil mastication (opening, closing, and total cycle time; opening and closing angles; and maximum velocity) also were evaluated. Repeated-measures analysis of variance in a generalized linear mixed models procedure was used for statistical analysis (α=.05). At baseline, participants with myofascial pain showed a reduced range of jaw motion and poorer sleep quality. Treatment with a stabilization device reduced pain (Pmastication increased, and improvements in sleep scores for the Pittsburgh Sleep Quality Index (P<.001) and Epworth Sleepiness Scale (P=.04) were found. Myofascial pain impairs jaw motion and quality of sleep; the reduction of pain after the use of a stabilization device improves the range of motion and sleep parameters. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  8. Sulfur Mustard Research—Strategies for the Development of Improved Medical Therapy

    Science.gov (United States)

    Kehe, Kai; Balszuweit, Frank; Emmler, Judith; Kreppel, Helmut; Jochum, Marianne; Thiermann, Horst

    2008-01-01

    Objective: Sulfur mustard (SM) is a bifunctional alkylating substance being used as chemical warfare agent (vesicant). It is still regarded as a significant threat in chemical warfare and terrorism. Exposure to SM produces cutaneous blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone marrow depression. Victims of World War I as well as those of the Iran-Iraq war have suffered from devastating chronic health impairment. Even decades after exposure, severe long-term effects like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and different forms of cancer have been diagnosed. Methods: This review briefly summarizes the scientific literature and own results concerning detection, organ toxicity of SM, its proposed toxicodynamic actions, and strategies for the development of improved medical therapy. Results: Despite extensive research efforts during the last century, efficient antidotes against SM have not yet been generated because its mechanism of action is not fully understood. However, deeper insights into these mechanisms gained in the last decade and promising developments of new drugs now offer new chances to minimize SM-induced organ damage and late effects. Conclusion: Polymerase inhibitors, anti-inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and probably regulators of DNA damage repair are identified as promising approaches to improve treatment. PMID:18615149

  9. Improving value in primary total joint arthroplasty care pathways: changes in inpatient physical therapy staffing.

    Science.gov (United States)

    Pelt, Christopher E; Anderson, Mike B; Pendleton, Robert; Foulks, Matthew; Peters, Christopher L; Gililland, Jeremy M

    2017-03-01

    An early physical therapy (PT) care pathway was implemented to provide same-day ambulation after total joint arthroplasty by changing PT staffing hours. After receiving an exemption from our institutional review board, we performed a secondary data analysis on a cohort of patients that underwent primary TJA of the hip or knee 6 months before and 12 months after implementation of the change. Data on same-day ambulation rates, length of stay (LOS), and in-hospital costs were reviewed. Early evaluation and mobilization of patients by PT improved on postoperative day (POD) 0 from 64% to 85% after the change ( P ≤ .001). The median LOS before the change was 3.27 days compared to 3.23 days after the change ( P  = .014). Patients with higher American Society of Anesthesiologists scores were less likely to ambulate on POD 0 ( P  = .038) and had longer hospital stays ( P < .001). Early mobilization in the entire cohort was associated with a greater cost savings ( P < .001). A relatively simple change to staffing hours, using resources currently available to us, and little additional financial or institutional investment resulted in a significant improvement in the number of patients ambulating on POD 0, with a modest reduction in both LOS and inpatient costs.

  10. Improving the segmentation of therapy-induced leukoencephalopathy using apriori information and a gradient magnitude threshold

    Science.gov (United States)

    Glass, John O.; Reddick, Wilburn E.; Reeves, Cara; Pui, Ching-Hon

    2004-05-01

    Reliably quantifying therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its varying MR properties and similarity to normal tissues and imaging artifacts. T1, T2, PD, and FLAIR images were analyzed for a subset of 15 children from an institutional protocol for the treatment of acute lymphoblastic leukemia. Three different analysis techniques were compared to examine improvements in the segmentation accuracy of leukoencephalopathy versus manual tracings by two expert observers. The first technique utilized no apriori information and a white matter mask based on the segmentation of the first serial examination of each patient. MR images were then segmented with a Kohonen Self-Organizing Map. The other two techniques combine apriori maps from the ICBM atlas spatially normalized to each patient and resliced using SPM99 software. The apriori maps were included as input and a gradient magnitude threshold calculated on the FLAIR images was also utilized. The second technique used a 2-dimensional threshold, while the third algorithm utilized a 3-dimensional threshold. Kappa values were compared for the three techniques to each observer, and improvements were seen with each addition to the original algorithm (Observer 1: 0.651, 0.653, 0.744; Observer 2: 0.603, 0.615, 0.699).

  11. Combined Therapy with Desferal and Deferiprone in Improvement of Heart Function in Thalassemic Patients

    Directory of Open Access Journals (Sweden)

    Shahramian Iraj

    2010-03-01

    Full Text Available Background: Cardiac complications due to iron overload are the most common causes of death in patients with major thalassemia. This study assessed the efficacy of iron chelating by desferal-L1 in improvement of cardiac function in patients with major thalassemia.Methods and Materials: Patients older then 8 years old with major thalassemia that were admitted to hematology ward of Ali-e-Asghar hospital of Zahedan in 2005-2006 and had lower than normal diastolic indices in annual echocardiography were considered as study population. During primary tests, indices of diastolic function of left and right hearts were calculated, using echocardiography with 2D, M-mode and Doppler then the patients were placed on a combination of desferal (30-40mg/kg/day two nights per week and L1 (deferiprone (75mg/kg/day, three times a day. At the end of the study, cardiac indices were calculated again. Data were using SPSS software and paired t-test and P0.05. Systolic indices of left ventricule increased significantly after treatment (P<0.05.Conclusion: In this study, after one year of treatment with a combination of desferal-L1 in patients with major thalassemia, echocardiography showed improvement in left heart systolic and diastolic function. This combination therapy prevented progression of right ventricular diastolic function abnormality