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

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.)

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).

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

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

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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.

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.

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

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.

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.

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.

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

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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

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

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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....

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

Combinatorial Effects of Arginine and Fluoride on Oral Bacteria

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Zheng, X.; Cheng, X.; Wang, L.; Qiu, W.; Wang, S.; Zhou, Y.; Li, M.; Li, Y.; Cheng, L.; Li, J.; Zhou, X.; Xu, X.

2015-01-01

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicati...

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.

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

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

2018-04-11

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

PRMT1-mediated arginine methylation controls ATXN2L localization

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Kaehler, Christian; Guenther, Anika; Uhlich, Anja; Krobitsch, Sylvia, E-mail: krobitsc@molgen.mpg.de

2015-05-15

Arginine methylation is a posttranslational modification that is of importance in diverse cellular processes. Recent proteomic mass spectrometry studies reported arginine methylation of ataxin-2-like (ATXN2L), the paralog of ataxin-2, a protein that is implicated in the neurodegenerative disorder spinocerebellar ataxia type 2. Here, we investigated the methylation state of ATXN2L and its significance for ATXN2L localization. We first confirmed that ATXN2L is asymmetrically dimethylated in vivo, and observed that the nuclear localization of ATXN2L is altered under methylation inhibition. We further discovered that ATXN2L associates with the protein arginine-N-methyltransferase 1 (PRMT1). Finally, we showed that neither mutation of the arginine–glycine-rich motifs of ATXN2L nor methylation inhibition alters ATXN2L localization to stress granules, suggesting that methylation of ATXN2L is probably not mandatory. - Highlights: • ATXN2L is asymmetrically dimethylated in vivo. • ATXN2L interacts with PRMT1 under normal and stress conditions. • PRMT1-mediated dimethylation of ATXN2L controls its nuclear localization. • ATXN2L localization to stress granules appears independent of its methylation state.

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

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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.

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

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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.

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

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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.

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.

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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.

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

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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.

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

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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.

Long-term Dental Visiting Patterns and Adult Oral Health

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Thomson, W.M.; Williams, S.M.; Broadbent, J.M.; Poulton, R.; Locker, D.

2010-01-01

To date, the evidence supporting the benefits of dental visiting comes from cross-sectional studies. We investigated whether long-term routine dental visiting was associated with lower experience of dental caries and missing teeth, and better self-rated oral health, by age 32. A prospective cohort study in New Zealand examined 932 participants’ use of dentistry at ages 15, 18, 26, and 32. At each age, routine attenders (RAs) were identified as those who (a) usually visited for a check-up, and (b) had made a dental visit during the previous 12 months. Routine attending prevalence fell from 82% at age 15 to 28% by 32. At any given age, routine attenders had better-than-average oral health, fewer had teeth missing due to caries, and they had lower mean DS and DMFS scores. By age 32, routine attenders had better self-reported oral health and less tooth loss and caries. The longer routine attendance was maintained, the stronger the effect. Routine dental attendance is associated with better oral health. PMID:20093674

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

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Jaffrezic-Renault N.

2012-12-01

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

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

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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.

Theoretical study about L-arginine complexes formation with thiotriazolin

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L. I. Kucherenko

2017-02-01

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

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

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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.

Functional and neurochemical profile of place learning after L-nitro-arginine in the rat

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Mogensen, Jesper; Wörtwein, Gitta; Hasman, Andreas

1995-01-01

Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning......Neurobiology, nitrogenoxid (NO), place learning, rotte, L-Nitro-Arginin, funktionel genopretning...

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

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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.)

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

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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.

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

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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.

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

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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.

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.

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

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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.

Short dental implants in patients with oral lichen planus: a long-term follow-up.

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Anitua, E; Piñas, L; Escuer-Artero, V; Fernández, R S; Alkhraisat, M H

2018-04-01

Oral lichen planus is associated with the Koebner phenomenon, and trauma may exacerbate oral lesions. Short dental implants, as alternatives to bony augmentation, would reduce the number of interventions and their morbidity. However, we know of no studies that have analysed the long-term outcomes of short implants in patients with oral lichen planus. We have therefore designed a retrospective study of such patients treated with short implants (≤8.5mm long), with survival of implants as the main outcome. The secondary outcomes were marginal bone loss and the development of complications. We calculated the implants' survival and compared the outcomes statistically between erosive and reticular oral lichen planus. Sixty-six short implants were placed in 23 patients with a mean (SD) age of 58 (7) years. The mean (SD) peri-implant bone loss was 0.96 (0.89) mm mesially and 0.99 (1.1) mm distally. Sixty-five of the 66 implants survived with a mean (SD) follow-up of 68 (32) months, and there were no significant differences between erosive and reticular disease. Stable long-term outcomes can be expected for short implants placed in patients with oral lichen planus, and graftless rehabilitation of missing teeth could be possible in these patients if short implants were used. Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

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....

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.

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.

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

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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.

Activities of daily living and oral hygiene status of older Korean patients in a long-term care facility.

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Seo, H-Y; Jeon, J-E; Chung, W-G; Kim, N-H

2017-05-01

This study investigated the relationship between oral hygiene conditions, activities of daily living (ADL) and cognitive ability in older Korean patients in long-term care facilities. Ninety older persons (65+) were randomly sampled from a possible 112 residents in a single facility. They participated in a 2-month-long survey. The Korean Modified Barthel Index was used to measure the ADL, and cognitive ability was measured using the Mini-Mental State Examination, Korean version. Oral hygiene status was measured using the Simplified Oral Hygiene Index and the Tongue Coating Index (TCI). Older participants with complete dependence manifested significantly poorer oral hygiene (P oral hygiene (P oral hygiene on tooth surfaces, while participants with partial dependence had poor tongue hygiene. In addition, dentulous older participants had poorer tongue hygiene than edentulous ones. This indicates the need to assess tooth status and provide oral care services via ADL in long-term care facilities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

Monitoring long-term oral corticosteroids.

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Mundell, Lewis; Lindemann, Roberta; Douglas, James

2017-01-01

Corticosteroids are synthetic analogues of human hormones normally produced by the adrenal cortex. They have both glucocorticoid and mineralocorticoid properties. The glucocortoid components are anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive. They influence the metabolism of carbohydrate and protein, in addition to playing a key role in the body's stress response. Mineralocorticoid's main significance is in the balance of salt and water concentrations. Due to the combination of these effects, corticosteroids can cause many adverse effects. Oral corticosteroids are absorbed systemically and are therefore more likely to cause adverse effects than topical or inhaled corticosteroids. Furthermore, it is assumed that greater duration of treatment will lead to a greater number of adverse effects, and therefore the most at risk group are those taking high dose, long-term oral corticosteroids (LTOC). High dose is defined as a prescription of >5 mg oral prednisolone and long term as duration of treatment >1 month (based on National Institute for Health and Care Excellence guidance for patient's 'at risk' of systemic side effects). Parameters to be monitored in primary care include weight, blood pressure, triglycerides, glucose and urea and electrolytes. From clinical experience within the general practice setting, the authors propose that these patients do not receive adequate baseline monitoring before starting corticosteroids nor are these markers monitored consistently thereafter. This project intended to evidence this claim, evaluate the adverse effect profile and improve monitoring in this patient group. The initial audit of 22 patients, within a single general practice, detected at least one documented adverse effect in 64% of patients, while 41% reported more than one adverse effect. 45% had recorded weight gain, 18% had recorded osteoporosis, 18% had at least one recorded cataract, 14% had recorded Hypertension, 14% had recorded

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.

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

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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.

Oral health care in older people in long term care facilities : A systematic review of implementation strategies

NARCIS (Netherlands)

Weening-Verbree, L.; Huisman-de Waal, G.; van Dusseldorp, L.; van Achterberg, T.; Schoonhoven, L.

Objectives: Oral hygiene is necessary to maintain oral health and quality of life. However, the oral hygiene and the oral health care of older people in long term care facilities are poor. This indicates that care is not in compliance with the available guidelines and protocols, and stresses the

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

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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.

Long-term effects of oral clefts on health care utilization

DEFF Research Database (Denmark)

Pedersen, Morten Saaby; Wehby, George L; Pedersen, Dorthe Almind

2015-01-01

clefts use more health services than their unaffected siblings. Additional results show that the effects are driven primarily by congenital malformation-related hospitalizations and intake of anti-infectives. Although the absolute differences in most health care utilization diminish over time, affected......Oral clefts are among the most common birth defects affecting thousands of newborns each year, but little is known about their potential long-term consequences. In this paper, we explore the impact of oral clefts on health care utilization over most of the lifespan. To account for time...... individuals have slightly higher utilization of some health care services in adulthood (particularly for diseases of the nervous and respiratory system). These results have important implications for affected individuals, their families, and their health professionals....

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.

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

Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes.

Science.gov (United States)

Abeles, Shira R; Ly, Melissa; Santiago-Rodriguez, Tasha M; Pride, David T

2015-01-01

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

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

Directory of Open Access Journals (Sweden)

B Rasoulian

2016-09-01

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

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...

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

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.

Long-term implant performance and patients' satisfaction in oligodontia

NARCIS (Netherlands)

Filius, Marieke A P; Vissink, Arjan; Cune, Marco S; Raghoebar, Gerry M; Visser, Anita

Objectives: To assess long-term (>= 10 years) implant survival, peri-implant health, patients' satisfaction and oral health related quality of life (OHQoL) in oligodontia patients rehabilitated with implant-based fixed prosthodontics. Methods: All oligodontia patients treated >= 10 years previously

Arginine metabolism by macrophages promotes cardiac and muscle fibrosis in mdx muscular dystrophy.

Directory of Open Access Journals (Sweden)

Michelle Wehling-Henricks

2010-05-01

Full Text Available Duchenne muscular dystrophy (DMD is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial

Short and long term modulation of tissue minerals concentrations following oral administration of black cumin (Nigella sativa L.) seed oil to laboratory rats.

Science.gov (United States)

Basheer, Irum; Qureshi, Irfan Zia

2018-01-15

Nigella sativa, or commonly called black cumin is a small herb of family Ranunculaceae is a well-known medicinal plant but its effects on tissue mineral concentrations of animal bodies is unknown. To study the effect of oral administration of fixed oil of black cumin seeds on tissues mineral content using laboratory rats as experimental model. Experimental animals were exposed to two oral doses of seed oil (60 and 120 ml kg -1 body weight). Short- and long term experiments lasted 24 h and 60 days respectively, with three replicates each. Oil extracted from black cumin seeds was subjected to GC-MS to identify chemical components. Following the wet digestion in nitric acid, samples of whole blood and organs of rats were subjected to atomic absorption spectrophotometry for determination of elements concentrations. Data were compared statistically at p < .05. Compared to control, Cr, Mn, Ni, Cu, Zn showed decrease, whereas Co, Na, Mg and K demonstrated increase, but Ca showed both increase and decrease in most of the tissues upon short term exposure to low and high doses of black cumin oil. During long term exposure, Cr, Fe, Mn, Cu exhibited decrease; Co, Na, Mg and Ca concentrations demonstrated an upregulation, whereas Ni and Zn showed increase and decrease in most of the tissues. Comparison of short term with long term experiments at low dose revealed increases in Fe, Zn, Cu, Mg, K and Ca, a decrease in Cr, Mn, Ni and Cu in most tissues, but both increase and decrease in Na. At high dose, an increase occurred in Fe, Ni, Zn, K, Ca, Mg, a decrease in Cr, while both increase and decrease in Cu, Co and Na concentrations. Our study demonstrates that oral administration of black cumin seeds oil to laboratory rats significantly alters tissue trace elements and electrolytes concentrations. The study appears beneficial but indicates modulatory role of black cumin oil as regards mineral metabolism with far reaching implications in health and disease. Copyright © 2017

The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D2 Dopamine Receptor (D2L-R Acts as an Intracellular Retention Signal

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Valentina Kubale

2016-07-01

Full Text Available This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D2 dopamine receptor (D2L-R confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR located within the insert could act as an RXR-type endoplasmic reticulum (ER retention signal. Arginine residues (R within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E, either individually or in clusters, thus generating single, double, and triple D2L-R mutants. Through analyses of cellular localization by confocal microscopy and enzyme-linked immunosorbent assay (ELISA, radioligand binding assay, bioluminescence resonance energy transfer (BRET2 β-arrestin 2 (βarr2 recruitment assay, and cAMP signaling, it was revealed that charge reversal of the R residues at all three positions within the motif impaired their colocalization with ER marker calnexin and led to significantly improved cell surface expression. Additionally, these data demonstrate that an R to glutamic acid (E substitution at position 2 within the RXR motif is not functionally permissible. Furthermore, all generated D2L-R mutants preserved their functional integrity regarding ligand binding, agonist-induced βarr2 recruitment and Gαi-mediated signaling. In summary, our results show that the conserved arginine cluster within the 29-amino acid insert of third cytoplasmic loop (IC3 of the D2L-R appears to be the ER retention signal.

Long-term Compliance with Oral 5-aminosalicylic Acid Therapy and Risk of Disease Recurrence in Patients with Ulcerative Colitis

DEFF Research Database (Denmark)

Prosberg, Michelle V; Vester-Andersen, Marianne K; Andersson, Mikael

2016-01-01

BACKGROUND: Noncompliance to long-term medical therapy is a well-known problem among patients treated for ulcerative colitis, but studies of long-term consequences in unselected patients are lacking. The authors aimed to determine the risk of recurrence according to long-term compliance with oral 5...

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

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.

The impact of oral health on body image and social interactions among elders in long-term care.

Science.gov (United States)

Donnelly, Leeann R; Clarke, Laura Hurd; Phinney, Alison; MacEntee, Michael I

2016-12-01

The objective of this study was to explore how social interactions and body image are influenced by perceived oral health among older people who live in long-term care facilities. Social interactions among frail elders in long-term care (LTC) facilities are limited, but to what extent body image and oral health influence their social relations is poorly understood. A positive body image and the perception of adequate oral health are linked to increased social contacts, as well as improved health and well-being irrespective of age. However, as frailty increases, it is unclear whether appearance and oral health priorities remain stable. Open-ended interviews were conducted with a purposefully selected group of cognitively intact, older men and women who exhibited varying degrees of frailty, social engagement and oral health conditions and lived in one of seven long-term care facilities. The interviews were analysed using a constant comparative technique, and a second interview with participants checked the trustworthiness of the analysis. Three major categories were expressed by the participants: (1) My mouth is fine; (2) It depends; and (3) Not that important. Within each category, there were several contributing and influencing factors. Social interactions among residents in LTC may be negatively impacted by poor oral health, but only if other personal and social issues are less bothersome than conditions with the mouth. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

The Effect of Pumpkin ( Cucurbita pepo L) Seeds and L-Arginine ...

African Journals Online (AJOL)

The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on androgenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in ...

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

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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.

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.

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).

Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine

DEFF Research Database (Denmark)

Orskov, C; Jeppesen, J; Madsbad, S

1991-01-01

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration...... integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed....... In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All...

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.

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.

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

Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

International Nuclear Information System (INIS)

Yu, Cheng-Chia; Chang, Yu-Chao

2013-01-01

Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

Enhancement of cancer stem-like and epithelial−mesenchymal transdifferentiation property in oral epithelial cells with long-term nicotine exposure: Reversal by targeting SNAIL

Energy Technology Data Exchange (ETDEWEB)

Yu, Cheng-Chia [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China); School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chang, Yu-Chao, E-mail: cyc@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China)

2013-02-01

Cigarette smoking is one of the major risk factors in the development and further progression of tumorigenesis, including oral squamous cell carcinoma (OSCC). Recent studies suggest that interplay cancer stem-like cells (CSCs) and epithelial−mesenchymal transdifferentiation (EMT) properties are responsible for the tumor maintenance and metastasis in OSCC. The aim of the present study was to investigate the effects of long-term exposure with nicotine, a major component in cigarette, on CSCs and EMT characteristics. The possible reversal regulators were further explored in nicotine-induced CSCs and EMT properties in human oral epithelial (OE) cells. Long-term exposure with nicotine was demonstrated to up-regulate ALDH1 population in normal gingival and primary OSCC OE cells dose-dependently. Moreover, long-term nicotine treatment was found to enhance the self-renewal sphere-forming ability and stemness gene signatures expression and EMT regulators in OE cells. The migration/cell invasiveness/anchorage independent growth and in vivo tumor growth by nude mice xenotransplantation assay was enhanced in long-term nicotine-stimulated OE cells. Knockdown of Snail in long-term nicotine-treated OE cells was found to reduce their CSCs properties. Therapeutic delivery of Si-Snail significantly blocked the xenograft tumorigenesis of long-term nicotine-treated OSCC cells and largely significantly improved the recipient survival. The present study demonstrated that the enrichment of CSCs coupled EMT property in oral epithelial cells induced by nicotine is critical for the development of OSCC tumorigenesis. Targeting Snail might offer a new strategy for the treatment of OSCC patients with smoking habit. -- Highlights: ► Sustained nicotine treatment induced CSCs properties of oral epithelial cells. ► Long-term nicotine treatment enhance EMT properties of oral epithelial cells. ► Long-term nicotine exposure increased tumorigenicity of oral epithelial cells. ► Si

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 ...

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

Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine Metabolism in Rats

Directory of Open Access Journals (Sweden)

Musalmah Mazlan

2017-01-01

Full Text Available Accumulating evidence suggests that altered arginine metabolism is involved in the aging and neurodegenerative processes. This study sought to determine the effects of age and vitamin E supplementation in the form of tocotrienol-rich fraction (TRF on brain arginine metabolism. Male Wistar rats at ages of 3 and 21 months were supplemented with TRF orally for 3 months prior to the dissection of tissue from five brain regions. The tissue concentrations of L-arginine and its nine downstream metabolites were quantified using high-performance liquid chromatography and liquid chromatography tandem mass spectrometry. We found age-related alterations in L-arginine metabolites in the chemical- and region-specific manners. Moreover, TRF supplementation reversed age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum. Multiple regression analysis revealed a number of significant neurochemical-behavioral correlations, indicating the beneficial effects of TRF supplementation on memory and motor function.

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

Science.gov (United States)

Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

2017-07-01

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

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

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

Efficacy of Long-Term Oral Vitamin B12 Supplementation after Total Gastrectomy: Results from a Prospective Study

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Joana Moleiro

2017-11-01

Full Text Available Background/Objectives: Vitamin B12 (VB12 deficiency is a common complication after total gastrectomy which may be associated with megaloblastic anemia and potentially irreversible neurologic symptoms. Intramuscular supplementation of VB12 has been considered the standard treatment, although it is associated with high costs and patient discomfort. Patients/Methods: We performed a prospective uncontrolled study (ACTRN12614000107628 in order to evaluate the clinical and laboratory efficacy of long-term oral VB12 supplementation in patients submitted to total gastrectomy. All patients received daily oral VB12 (1 mg/day and were evaluated every 3 months (clinical and laboratory evaluation: hemoglobin, VB12, total iron, ferritin, and folate. Results: A total of 26 patients were included with a mean age of 64 years (29-79. Patients were included with a mean period of 65 months (3-309 after total gastrectomy. At inclusion time, 17/26 patients were under intramuscular VB12, and 9 had not started supplementation yet. There were normal serum VB12 levels in 25/26 patients (mean VB12 serum levels: 657 pg/mL. The mean follow-up period was 20 (8.5-28 months. During follow-up, all patients had normal VB12 levels and there was no need for intramuscular supplementation. The patient with low VB12 levels had an increase to adequate levels, which remained stable. There were no differences with statistical significance among VB12 levels at 6 (867 pg/mL, 12 (1,008 pg/mL, 18 (1,018 pg/mL, and 24 (1,061 pg/mL months. Iron and folate supplementation was necessary in 21 and 7 patients, respectively. Conclusions: Oral VB12 supplementation is effective and safe in patients who underwent total gastrectomy and should be considered the preferential form of supplementation.

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

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

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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....

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

OpenAIRE

Wen-bin He; Kazuho Abe; Tatsuhiro Akaishi

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to...

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

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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...

Racial differences in long-term adherence to oral antidiabetic drug therapy: a longitudinal cohort study

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Meigs James B

2009-02-01

Full Text Available Abstract Background Adherence to oral antidiabetic medications is often suboptimal. Adherence differences may contribute to health disparities for black diabetes patients, including higher microvascular event rates, greater complication-related disability, and earlier mortality. Methods In this longitudinal retrospective cohort study, we used 10 years of patient-level claims and electronic medical record data (1/1/1992–12/31/2001 to assess differences in short- and long-term adherence to oral antidiabetic medication among 1906 newly diagnosed adults with diabetes (26% black, 74% white in a managed care setting in which all members have prescription drug coverage. Four main outcome measures included: (1 time from diabetes diagnosis until first prescription of oral antidiabetic medication; (2 primary adherence (time from first prescription to prescription fill; (3 time until discontinuation of oral antidiabetic medication from first prescription; and (4 long-term adherence (amount dispensed versus amount prescribed over a 24-month follow-up from first oral antidiabetic medication prescription. Results Black patients were as likely as whites to initiate oral therapy and fill their first prescription, but experienced higher rates of medication discontinuation (HR: 1.8, 95% CI: 1.2, 2.7 and were less adherent over time. These black-white differences increased over the first six months of therapy but stabilized thereafter for patients who initiated on sulfonylureas. Significant black-white differences in adherence levels were constant throughout follow-up for patients initiated on metformin therapy. Conclusion Racial differences in adherence to oral antidiabetic drug therapy persist even with equal access to medication. Early and continued emphasis on adherence from initiation of therapy may reduce persistent racial differences in medication use and clinical outcomes.

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.

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo

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Wen-bin He

2018-01-01

Full Text Available To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood–brain barrier and promotes synaptic functions in the hippocampus.

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.

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

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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.

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

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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.

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.

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.

Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats

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Lauren Izabel Medeiros Couto

2015-08-01

Full Text Available ABSTRACTOBJECTIVE: To evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats. METHODS: Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG, after induction of injuries, the rats were observed for 24 h. In the simulation group (SG and the arginine group (AG respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK, lactic dehydrogenase (LDH, aspartate aminotransferase (AST and C-reactive protein (CRP. The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's tmethods were used and p≤ 0.05 was taken to be statistically significant. RESULTS: In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis. CONCLUSION: Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain.

Resveratrol Based Oral Nutritional Supplement Produces Long-Term Beneficial Effects on Structure and Visual Function in Human Patients

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Stuart Richer

2014-10-01

Full Text Available Background: Longevinex® (L/RV is a low dose hormetic over-the-counter (OTC oral resveratrol (RV based matrix of red wine solids, vitamin D3 and inositol hexaphosphate (IP6 with established bioavailability, safety, and short-term efficacy against the earliest signs of human atherosclerosis, murine cardiac reperfusion injury, clinical retinal neovascularization, and stem cell survival. We previously reported our short-term findings for dry and wet age-related macular degeneration (AMD patients. Today we report long term (two to three year clinical efficacy. Methods: We treated three patients including a patient with an AMD treatment resistant variant (polypoidal retinal vasculature disease. We evaluated two clinical measures of ocular structure (fundus autofluorescent imaging and spectral domain optical coherence extended depth choroidal imaging and qualitatively appraised changes in macular pigment volume. We further evaluated three clinical measures of visual function (Snellen visual acuity, contrast sensitivity, and glare recovery to a cone photo-stress stimulus. Results: We observed broad bilateral improvements in ocular structure and function over a long time period, opposite to what might be expected due to aging and the natural progression of the patient’s pathophysiology. No side effects were observed. Conclusions: These three cases demonstrate that application of epigenetics has long-term efficacy against AMD retinal disease, when the retinal specialist has exhausted other therapeutic modalities.

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...

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

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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

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands

NARCIS (Netherlands)

S. Fazeli Farsani; P. Souverein (Patrick); J.A. Overbeek (Jetty); M.M.J. Van Der Vorst; C.A.J. Knibbe (Catherijne); R.M.C. Herings (Ron); A.C. de Boer (Anton); A.K. Mantel-Teeuwisse (Aukje)

2015-01-01

textabstractAim The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. Methods A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at

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.

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.

Long-term stability of intra-oral maxillary distraction in unilateral cleft lip and palate: a case report.

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Nevzatoğlu, Sirin; Küçükkeleş, Nazan; Güzel, Zeki

2013-11-01

This case report presents short and long-term treatment results of a unilateral cleft lip and palate patient treated with a modified intra-oral tooth-bone borne distraction appliance. The chief complaints of a 16 year-old, unilateral cleft lip and palate patient were poor facial aesthetics, crowding and a fistula. Severe maxillary retrognathism was treated via distraction osteogenesis of the maxilla and performed using an intra-oral tooth-bone borne appliance. Treatment continued to completion with a multibracket system. At an eight-year review following the distraction procedure, the short and long-term results were determined cephalometrically. Following the distraction, A-point advanced 7 mm, 2 mm of which relapsed during fixed appliance treatment. At the end of the active treatment, the patient's skeletal and dental Class III relationship improved to Class I, which was preserved at the long-term review. The profile was markedly improved by the distraction osteogenesis. In cases of severe maxillary retrognathism as a result of a cleft lip and palate, maxillary distraction osteogenesis provides a viable alternative to orthognathic surgery.

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

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands

NARCIS (Netherlands)

Fazeli Farsani, S; Souverein, P C; Overbeek, J A; van der Vorst, M M J; Knibbe, C A J; Herings, R M C; de Boer, Anthonius; Mantel-Teeuwisse, A K

AIM: The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. METHODS: A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at least one

Oral administration of fisetin promotes the induction of hippocampal long-term potentiation in vivo.

Science.gov (United States)

He, Wen-Bin; Abe, Kazuho; Akaishi, Tatsuhiro

2018-01-01

To explore memory enhancing effect of the flavonoid fisetin, we investigated the effect of oral administration of flavonoids on the induction of long-term potentiation (LTP) at hippocampal CA1 synapses of anesthetized rats. Among four flavonoids (fisetin, quercetin, luteolin and myricetin) tested, only fisetin significantly facilitated the induction of hippocampal LTP. The effect of oral fisetin was abolished by intracerebroventricular injection of U0126, an agent that was previously found to inhibit its effect in hippocampal slices in vitro. These results suggest that orally administered fisetin crosses the blood-brain barrier and promotes synaptic functions in the hippocampus. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles

Directory of Open Access Journals (Sweden)

Ni Chen

2016-06-01

Full Text Available Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20–30 nm with different surface coatings to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT, bare Ag NP (Ag-B, and poly (N-vinyl-2-pyrrolidone-coated Ag NP (Ag-PVP. The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level. The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

[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.

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

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

Nutritional supplementation with arginine protects radiation-induced effects: an experimental study

Energy Technology Data Exchange (ETDEWEB)

Pinto, Flavia Cristina Morone, E-mail: fcmorone@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco Jose Barcellos [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil)

2016-10-15

Purpose: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Methods: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. Results: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Conclusions: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine. (author)

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

Science.gov (United States)

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

2012-11-01

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

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

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...

Enhancement of brain serotonin by long term oral administration of tryptophan produces no effect on food intake

International Nuclear Information System (INIS)

Haider, S.; Akhtar, N.; Kidwai, I.M.; Haleem, D.J.

1999-01-01

L-tryptophan (TRP) is widely used to enhance serotonin mediate brain functions. In the Present study effects of oral administration of TRP (100mg/kg) daily for 5 weeks, were investigated on the food intake, growth rate and brain indole amine metabolism in young rats. TRP ingestion significantly increased growth rate but did not alter food intake in rats. The levels of TRP and 5-hydroxytryptamine (5-HT) were higher in the hypothalamus of TRP treated rats. Increases of 5-hydroxyindole acetic acid (5-HIAA) were hot significant. TRP, 5-HT and 5-HIAA all increased in the rest of the brain of TRP treated rats. The present study shows that long term TRP administration thorough increases brain 5-ht metabolism and turnover but functional responses to 5-ht are not necessarily increases. (author)

Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2014-11-01

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical.

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.

PROUD: Effects of preoperative long-term immunonutrition in patients listed for liver transplantation

Directory of Open Access Journals (Sweden)

Büchler Markus W

2007-08-01

Full Text Available Abstract Background Patients with end stage liver disease are characteristically malnourished which is associated with poor outcome. Formulas enriched with arginine, ω-3 fatty acids, and nucleotides, "immunonutrients", potentially improve their nutritional status. This study is designed to evaluate the clinical outcome of long-term "immunonutrition" of patients with end-stage liver disease while on the waiting list for liver transplantation. Methods/design A randomized controlled double blind multi-center clinical trial with two parallel groups comprising a total of 142 newly registered patients for primary liver transplantation has been designed to assess the safety and efficacy of the long-term administration of ORAL IMPACT®, an "immunonutrient" formula, while waiting for a graft. Patients will be enrolled the day of registration on the waiting list for liver transplantation. Study ends on the day of transplantation. Primary endpoints include improved patients' nutritional and physiological status, as measured by mid-arm muscle area, triceps skin fold thickness, grip strength, and fatigue score, as well as patients' health related quality of life. Furthermore, patients will be followed for 12 postoperative weeks to evaluate anabolic recovery after transplantation as shown by reduced post-transplant mechanical ventilation, hospital stay, wound healing, infectious morbidities (pneumonia, intraabdominal abscess, sepsis, line sepsis, wound infection, and urinary tract infection, acute and chronic rejection, and mortality. Discussion Formulas enriched with arginine, ω-3 fatty acids, and nucleotides have been proven to be beneficial in reducing postoperative infectious complications and length of hospital stay among the patients undergoing elective gastrointestinal surgery. Possible mechanisms include downregulation of the inflammatory responses to surgery and immune modulation rather than a sole nutritional effect. Trial registration Clinical

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.

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.

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.

Effects of short term and long term Extremely Low Frequency Magnetic Field on depressive disorder in mice: Involvement of nitric oxide pathway.

Science.gov (United States)

Madjid Ansari, Alireza; Farzampour, Shahrokh; Sadr, Ali; Shekarchi, Babak; Majidzadeh-A, Keivan

2016-02-01

Previous reports on the possible effects of Extremely Low Frequency Magnetic Fields (ELF MF) on mood have been paradoxical in different settings while no study has yet been conducted on animal behavior. In addition, it was shown that ELF MF exposure makes an increase in brain nitric oxide level. Therefore, in the current study, we aimed to assess the possible effect(s) of ELF MF exposure on mice Forced Swimming Test (FST) and evaluate the probable role of the increased level of nitric oxide in the observed behavior. Male adult mice NMRI were recruited to investigate the short term and long term ELF MF exposure (0.5 mT and 50 Hz, single 2h and 2 weeks 2h a day). Locomotor behavior was assessed by using open-field test (OFT) followed by FST to evaluate the immobility time. Accordingly, NΩ-nitro-l-arginine methyl ester 30 mg/kg was used to exert anti-depressant like effect. According to the results, short term exposure did not alter the immobility time, whereas long term exposure significantly reduces immobility time (pmice, whereas short term exposure has no significant effect. Also, reversing the anti-depressant activity of L-NAME indicates a probable increase in the brain nitric oxide. Copyright © 2016 Elsevier Inc. All rights reserved.

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 ...

Long-term use of short- and long-acting nitrates in stable angina pectoris.

Science.gov (United States)

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

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.

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.

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

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

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.

[Dental care and oral hygiene practices in long-term geriatric care institutions].

Science.gov (United States)

Ferreira, Raquel Conceição; Schwambach, Carolina Wolff; de Magalhães, Cláudia Silami; Moreira, Allyson Nogueira

2011-04-01

This study evaluated the activities of dentists, dental care and oral hygiene practices in the long-term care institutions of Belo Horizonte (Minas Gerais, Brazil). A semi-structured questionnaire was handed out to the coordinators of 37 philanthropic and 30 private institutions. The data was compared by the chi-square and Fisher's Exact Tests. 81% of the questionnaires were answered. The majority of the private (74.2%) and philanthropic institutions (87%) do not have a dentist (p=0.21). The location, period of existence, type institution kind and number of residents weren't factors regarding the presence of a dentist (p>0.05). 67% of the philanthropic institutions with equipped consultation rooms had dentists, though there were none when there was no consultation room. Even without consultation rooms, 13% of the private institutions had dentists. When necessary, 69.6% of the philanthropic institutions refer the elderly to public health centers, while 58.1% of the private institutions refer them to their family dentists. A higher percentage of the private institutions adopted systematic oral hygiene procedures (p=0.01), with a considerable divergence of treatment reported. There is a need to include a dentist on the health staff in the institutions and for systematization of oral hygiene practices.

Oral health status among long-term hospitalized adults: a cross sectional study

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Leon Bilder

2014-06-01

Full Text Available Background. Many Long-Term Care (LTC institutionalized patients are the most frail and functionally dependent among the geriatric population and have significant oral health disparities.They often suffer from dental neglect due to limited access to appropriate professional dental care. These patients have chronic health situations and are treated with medications, which increase their risk of oral diseases. Despite the growth in elderly population in Israel, there is insufficient data regarding their oral health status and treatment needs.Objective. To describe the oral health status of the LTC hospitalized adults in a geriatric and psychiatric hospital in Israel.Methods. Data was recorded from LTC hospitalized adults with a physical and/or mental disabilities in a cross-sectional research design, which included general health anamnesis and clinical oral examination. Variables included gender, medicines, oral hygiene (OH, using dentures, number of caries lesions and residual teeth. Univariate analyses included Pearson χ2 and t-test analyses. Multivariate analyses included logistic and linear regressions while the outcome variables were categorical OH index and number of carious cavitations, number of residual teeth and carious teeth percentage.Results. 153 participants were included in the study with a mean age of 65.03 ± 18.67 years. 31.3% of the patients were edentulous, and only 14% had partial or full dentures. Females had a significantly higher number of caries cavitation than males (P = 0.044. The number of caries cavitation was higher among patients with poor OH (P < 0.001 and when taking Clonazepam (P = 0.018. Number of residual teeth was higher in the fair OH group (P < 0.001. Carious teeth percentage was higher among the poor OH group (P < 0.001.

Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine.

Science.gov (United States)

Berninger, Teresa; Bliem, Christina; Piccinini, Esteban; Azzaroni, Omar; Knoll, Wolfgang

2018-09-15

Herein, a biosensor based on a reduced graphene oxide field effect transistor (rGO-FET) functionalized with the cascading enzymes arginase and urease was developed for the detection of L-arginine. Arginase and urease were immobilized on the rGO-FET sensing surface via electrostatic layer-by-layer assembly using polyethylenimine (PEI) as cationic building block. The signal transduction mechanism is based on the ability of the cascading enzymes to selectively perform chemical transformations and prompt local pH changes, that are sensitively detected by the rGO-FET. In the presence of L-arginine, the transistors modified with (PEI/urease(arginase)) multilayers showed a shift in the Dirac point due to the change in the local pH close to the graphene surface, produced by the catalyzed urea hydrolysis. The transistors were able to monitor L-arginine in the 10-1000 μM linear range with a LOD of 10 μM, displaying a fast response and a good long-term stability. The sensor showed stereospecificity and high selectivity in the presence of non-target amino acids. Taking into account the label-free, real-time measurement capabilities and the easily quantifiable, electronic output signal, this biosensor offers advantages over state-of-the-art L-arginine detection methods. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Long-term Nasal and Peri-oral Tightening by a Single Fractional Noninsulated Microneedle Radiofrequency Treatment.

Science.gov (United States)

Tanaka, Yohei

2017-02-01

Background: The skin tightening effects induced by non-insulated microneedle radiofrequency have proved long-lasting. Our previous three-dimensional volumetric assessment showed significant facial tightening for up to six months. However, nasal and peri-oral tightening effects lasted longer. The objective of this study was to investigate the distribution of the long-term volumetric reduction in facial area induced by a single fractional non-insulated microneedle radiofrequency treatment. Methods: Fifteen Asian patients underwent full facial skin tightening using a sharply tapered non-insulated microneedle radiofrequency applicator with a novel fractionated pulse mode. Three-dimensional volumetric assessments were performed at six and 12 months post-treatment. Patients rated their satisfaction using a 5-point scale at each follow up. Results: Objective assessments with superimposed three-dimensional color images showed significant volumetric reduction in the nasal and peri-oral areas at 12 months post-treatment in all patients. Median volumetric reductions at six and 12 months post-treatment were 13.1 and 12.3ml, respectively. All of the patients were satisfied with their results 12 months post-treatment. Side effects were not observed. Conclusions: This single fractional NIMNRF treatment provided long-lasting nasal and peri-oral tightening as shown via 3D volumetric assessment. Moreover, NIMNRF produced minimal complications, downtime, and few side effects. This approach provides safe and effective treatment of skin tightening.

Effect of Long-term Smoking on Whole-mouth Salivary Flow Rate and Oral Health.

Science.gov (United States)

Rad, Maryam; Kakoie, Shahla; Niliye Brojeni, Fateme; Pourdamghan, Nasim

2010-01-01

Change in the resting whole-mouth salivary flow rate (SFR) plays a significant role in patho-genesis of various oral conditions. Factors such as smoking may affect SFR as well as the oral and dental health. The primary purpose of this study was to determine the effect of smoking on SFR, and oral and dental health. One-hundred smokers and 100 non-tobacco users were selected as case and control groups, respectively. A questionnaire was used to collect the demographic data and smoking habits. A previously used questionnaire about dry mouth was also employed. Then, after a careful oral examination, subjects' whole saliva was collected in the resting condition. Data was analyzed by chi-square test using SPSS 15. The mean (±SD) salivary flow rate were 0.38 (± 0.13) ml/min in smokers and 0.56 (± 0.16) ml/min in non-smokers. The difference was statistically significant (P=0.00001). Also, 39% of smokers and 12% of non-smokers reported experiencing at least one xerostomia symptom, with statistically significant difference between groups (p=0.0001). Oral lesions including cervical caries, gingivitis, tooth mobility, calculus and halitosis were significantly higher in smokers. Our findings indicated that long-term smoking would significantly reduce SFR and increase oral and dental disorders associated with dry mouth, especially cervical caries, gingivitis, tooth mobility, calculus, and halitosis.

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...

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.

Randomized clinical trial of arginine-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing gastric cancer surgery.

Science.gov (United States)

Zhao, Hongyan; Zhao, Hongying; Wang, Yu; Jing, Huang; Ding, Qian; Xue, Jun

2013-09-01

Significant malnutrition exists in a high percentage of patients with gastric cancer. It is, therefore, crucial to establish an effective means to provide nutrition for these patients. This prospective, randomized, double-blinded clinical trial aims to assess the long-term survival of arginine-supplementation enteral nutrition versus standard enteral nutrition in malnourished patients with gastric cancer. The control group (36 cases) received postoperative standard enteral nutrition. Meanwhile, the arginine-supplementation group (37 cases) adopted the same nutrition product but enriched with arginine (9.0 g/L). The primary study objective was overall survival (OS). Secondary endpoints were progression-free survival (PFS); serum parameters including total protein, albumin, proalbumin, and transferrin obtained on preoperative day 1, postoperative day 2, and day 12; CD4(+) and CD8(+) T cells, natural killer (NK) cells, immunoglobulin M (IgM), and immunoglobulin G (IgG) obtained on preoperative day 1 and postoperative day 7. No significant differences in baseline characteristics were observed between groups. The group receiving arginine-enriched nutrition had a significantly better OS (P = 0.03, 41 vs. 30.5 months) and better PFS (P = 0.02, 18 vs. 11.5 months). On postoperative day 7, CD4(+) T cells, NK cells, IgM and IgG levels of the arginine-supplemented group increased prominently and were significantly higher than those of the control group and those on preoperative day 1. There is no significant difference in the serum total protein, albumin, proalbumin, and transferrin levels between the two arms. Arginine-supplemented enteral nutrition significantly improves long-term survival and restores immunity in malnourished gastric cancer.

Successive oral immunizations against Piscirickettsia salmonis and infectious salmon anemia virus are required to maintain a long-term protection in farmed salmonids

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Ivan eTobar

2015-05-01

Full Text Available Currently, there is a growing demand to determine the protective status of vaccinated fish in order to prevent diseases outbreaks. A set of different parameters that include the infectious and immunological status of vaccinated salmonids from 622 Chilean farms were analyzed during 2011-2014. The aim of this study was to optimize the vaccination program of these centers through the determination of the protective state of vaccinated fish using oral immunizations. This state was measured by the association of the concentration of the immunoglobulin M (IgM in the serum and the mortality rate of vaccinated fish. Salmonids were vaccinated with different commercial mono- or polyvalent vaccines against SRS and ISAv, first by the intraperitoneal injection of oil-adjuvanted antigens and then by the stimulation of mucosal immunity using oral vaccines as booster. The results showed that high levels of specific IgM antibodies were observed after injectable vaccination, reaching a maximum concentration at 600-800 degree-days. Similar levels of antibodies were observed when oral immunizations were administrated. The high concentration of antibodies (above 2750 ng/mL for ISAv and 3500 ng/mL for SRS was maintained for a period of 800 degree-days after each vaccination procedure. In this regard, oral immunizations maintained a long-term high concentration of anti-SRS and anti-ISAv specific IgM antibodies. When the concentration of antibodies decreased below 2000 pg/mL, a window of susceptibility to SRS infection was observed in the farm, suggesting the close association between antibody levels and fish protective status. These results demonstrated that, in the field, several oral immunizations are essential to uphold a high level of specific anti-pathogens antibodies and, therefore, a protective status during the whole productive cycle.

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.

The effect of pumpkin (Cucurbita pepo L) seeds and L-arginine supplementation on serum lipid concentrations in atherogenic rats.

Science.gov (United States)

Abuelgassim, Abuelgassim O; Al-showayman, Showayman I A

2012-01-01

The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on atherogenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in drinking water and the other supplemented with pumpkin seeds in diet at a concentration equivalent to 2% arginine. Supplementation continued for 37 days. Atherogenic rats supplemented with pumpkin seeds showed a significant decrease (ppumpkin seeds significantly decreased serum concentrations of TC and LDL-C. Our findings suggest that pumpkin seeds supplementation has a protective effect against atherogenic rats and this protective effect was not attributed to the high arginine concentrations in pumpkin seeds.

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.

Nursing Administrators' Views on Oral Health in Long-Term Care Facilities: An exploratory study.

Science.gov (United States)

Urata, Janelle Y; Couch, Elizabeth T; Walsh, Margaret M; Rowe, Dorothy J

2018-04-01

Purpose: To explore the knowledge, attitudes, and practices of supervising nurse administrators (SNAs) regarding the oral care provided to long-term care facility (LTCF) residents and the role of dental professionals in those facilities. Methods: The investigators of this study partnered with the National Association of Nursing Administrators to send this cross-sectional study consisting of a 35-item electronic survey to its members whose email addresses were in their database. Online software tabulated responses and calculated frequencies (percentages) of responses for each survey item. Results: Of the 2,359 potential participants, 171 (n=171) completed the survey for a 7% response rate. Only 25% of the respondents were familiar with the expertise of dental hygienists (DHs), however once informed, the majority were interested in having DHs perform oral health staff trainings, oral screenings, and dental referrals and initiate fluoride varnish programs. Most respondents correctly answered the oral health-related knowledge items, understood that oral health is important to general health, but reported that the LTCF residents' oral health was only "good" or "fair." Fewer than half, (48%) of the SNAs were "very satisfied" with the quality of oral care provided to the residents. While more than half reported that they had no dentist on staff or on-site dental equipment, 77% reported that they would consider on-site mobile oral care services. Oral health training for staff was provided primarily by registered nurses, however only 32% reported including identification of dental caries as part of the in-service training. Conclusion: This exploratory study lays the foundation for more extensive research investigating various strategies to improve the oral health of LTCF residents, including increased collaboration between DHs and SNAs. Copyright © 2018 The American Dental Hygienists’ Association.

Effect of Long-term Smoking on Whole-mouth Salivary Flow Rate and Oral Health

Directory of Open Access Journals (Sweden)

Maryam Rad

2010-12-01

Full Text Available Background and aims. Change in the resting whole-mouth salivary flow rate (SFR plays a significant role in pathogenesis of various oral conditions. Factors such as smoking may affect SFR as well as the oral and dental health. The primary purpose of this study was to determine the effect of smoking on SFR, and oral and dental health. Materials and methods. One-hundred smokers and 100 non-tobacco users were selected as case and control groups, respectively. A questionnaire was used to collect the demographic data and smoking habits. A previously used questionnaire about dry mouth was also employed. Then, after a careful oral examination, subjects’ whole saliva was collected in the resting condition. Data was analyzed by chi-square test using SPSS 15. Results. The mean (±SD salivary flow rate were 0.38 (± 0.13 ml/min in smokers and 0.56 (± 0.16 ml/min in nonsmokers. The difference was statistically significant (P=0.00001. Also, 39% of smokers and 12% of non-smokers reported experiencing at least one xerostomia symptom, with statistically significant difference between groups (p=0.0001. Oral lesions including cervical caries, gingivitis, tooth mobility, calculus and halitosis were significantly higher in smokers. Conclusion. Our findings indicated that long-term smoking would significantly reduce SFR and increase oral and dental disorders associated with dry mouth, especially cervical caries, gingivitis, tooth mobility, calculus, and halitosis.

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.

The Long-Term Effects of Chemo Radiotherapy on Oral Health and Dental Development in Childhood Cancer

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J. Momenbeitollahi

2011-03-01

Full Text Available The improvement in survival and local control measures in children with neoplasm in the head and neck region may lead to increased iatrogenic adverse effects of treatment. The aim of this study was to report a new case of the long-term effects of chemoradiotherapyon oral health and dental development in a patient treated for Hodgkin’s disease at an early age. In this case report, a 26-year-old female is presented, who at the age of 5 years receivedchemotherapy and radiotherapy for Hodgkin’s disease in the neck region. The patient consulted the Department of Oral Medicine because of dental changes and tooth loss despite adequate dental care and oral hygiene. Clinical examination revealed loose teethand inflamed gingiva of the mandible, x-ray showed premature root resorption, V-shaped and shortened roots and alveolar bone loss. After examination, the patient was referred for extracting the mandibular teeth and then wassent to the prosthetics department. Therefore,in order to decrease dental treatment sequelae in patients who have had cured malignant disease, these cases should have life-long dental care and follow-up.

Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats.

Science.gov (United States)

Mohebbati, Reza; Bavarsad, Kosar; Rahimi, Maryam; Rakhshandeh, Hasan; Khajavi Rad, Abolfazl; Shafei, Mohammad Naser

2018-01-01

Ziziphus jujuba stimulates the release of nitric oxide (NO). Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28 th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups. In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (pL-NAME group (p>0.05). Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency.

Population pharmacokinetic model of THC integrates oral, intravenous, and pulmonary dosing and characterizes short- and long-term pharmacokinetics.

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Heuberger, Jules A A C; Guan, Zheng; Oyetayo, Olubukayo-Opeyemi; Klumpers, Linda; Morrison, Paul D; Beumer, Tim L; van Gerven, Joop M A; Cohen, Adam F; Freijer, Jan

2015-02-01

Δ(9)-Tetrahydrocannobinol (THC), the main psychoactive compound of Cannabis, is known to have a long terminal half-life. However, this characteristic is often ignored in pharmacokinetic (PK) studies of THC, which may affect the accuracy of predictions in different pharmacologic areas. For therapeutic use for example, it is important to accurately describe the terminal phase of THC to describe accumulation of the drug. In early clinical research, the THC challenge test can be optimized through more accurate predictions of the dosing sequence and the wash-out between occasions in a crossover setting, which is mainly determined by the terminal half-life of the compound. The purpose of this study is to better quantify the long-term pharmacokinetics of THC. A population-based PK model for THC was developed describing the profile up to 48 h after an oral, intravenous, and pulmonary dose of THC in humans. In contrast to earlier models, the current model integrates all three major administration routes and covers the long terminal phase of THC. Results show that THC has a fast initial and intermediate half-life, while the apparent terminal half-life is long (21.5 h), with a clearance of 38.8 L/h. Because the current model characterizes the long-term pharmacokinetics, it can be used to assess the accumulation of THC in a multiple-dose setting and to forecast concentration profiles of the drug under many different dosing regimens or administration routes. Additionally, this model could provide helpful insights into the THC challenge test used for the development of (novel) compounds targeting the cannabinoid system for different therapeutic applications and could improve decision making in future clinical trials.

Improving oral hygiene in the long-term care of the elderly--a RCT.

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Zenthöfer, Andreas; Dieke, Reinhard; Dieke, Anke; Wege, Karl-Christian; Rammelsberg, Peter; Hassel, Alexander J

2013-06-01

Oral hygiene and health of the institutionalized elderly are frequently described as inadequate. This randomized and single-blinded (outcome evaluation) study compared three types of intervention for improving oral hygiene with a control. The purpose was to investigate whether there were any significant differences between the intervention and control groups. One hundred and six participants living in long-term care homes in South-West Germany were recruited and randomly divided into four groups-three therapy groups and one control group. For all three therapy groups, teeth and dentures were cleaned professionally and individual instruction was given. One of these groups was also re-instructed and remotivated by a dentist (n = 27). One also received help from, and was remotivation by, staff educated in dental hygiene (n = 26). The third therapy group was not remotivated after professional cleaning of teeth and dentures (n = 26). For the control group, there was no intervention (n = 23). The main target clinical data were mean plaque (plaque-control record, O'Leary), gingival bleeding (Ainamo/Bay), and denture hygiene indices. For assessment of the difference between being in an intervention group and in a control group, mixed-model analysis for repeated measurements was performed for each main target variable. In addition, target clinical data were evaluated in long-term follow-up after 3 years. Compared with controls, denture hygiene, plaque, and gingival bleeding indices were significantly lower in the intervention groups over a twelve-week period (mixed model for repeated measurements; P hygiene. However, the effect decreases over time and renewal of the intervention is necessary. © 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

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

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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.

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

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Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

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

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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.

Human Primary Epithelial Cells Acquire an Epithelial-Mesenchymal-Transition Phenotype during Long-Term Infection by the Oral Opportunistic Pathogen, Porphyromonas gingivalis

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Jungnam Lee

2017-12-01

Full Text Available Porphyromonas gingivalis is a host-adapted oral pathogen associated with chronic periodontitis that successfully survives and persists in the oral epithelium. Recent studies have positively correlated periodontitis with increased risk and severity of oral squamous cell carcinoma (OSCC. Intriguingly, the presence of P. gingivalis enhances tumorigenic properties independently of periodontitis and has therefore been proposed as a potential etiological agent for OSCC. However, the initial host molecular changes induced by P. gingivalis infection which promote predisposition to cancerous transformation through EMT (epithelial-mesenchymal-transition, has never been studied in human primary cells which more closely mimic the physiological state of cells in vivo. In this study, we examine for the first time in primary oral epithelial cells (OECs the expression and activation of key EMT mediators during long-term P. gingivalis infection in vitro. We examined the inactive phosphorylated state of glycogen synthase kinase-3 beta (p-GSK3β over 120 h P. gingivalis infection and found p-GSK3β, an important EMT regulator, significantly increases over the course of infection (p < 0.01. Furthermore, we examined the expression of EMT-associated transcription factors, Slug, Snail, and Zeb1 and found significant increases (p < 0.01 over long-term P. gingivalis infection in protein and mRNA expression. Additionally, the protein expression of mesenchymal intermediate filament, Vimentin, was substantially increased over 120 h of P. gingivalis infection. Analysis of adhesion molecule E-cadherin showed a significant decrease (p < 0.05 in expression and a loss of membrane localization along with β-catenin in OECs. Matrix metalloproteinases (MMPs 2, 7, and 9 are all markedly increased with long-term P. gingivalis infection. Finally, migration of P. gingivalis infected cells was evaluated using scratch assay in which primary OEC monolayers were wounded and treated with

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

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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.

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

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

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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.

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

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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.

Long-term effects of Class II orthodontic treatment on oral health.

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Bock, N C; Saffar, M; Hudel, H; Evälahti, M; Heikinheimo, K; Rice, D P C; Ruf, S

2018-03-01

To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

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

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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

Robust GLP-1 secretion by basic L-amino acids does not require the GPRC6A receptor

DEFF Research Database (Denmark)

Clemmensen, Christoffer; Jørgensen, Christinna V; Smajilovic, Sanela

2017-01-01

(GLP-1) secretion is unclear. Therefore, to probe if the GPRC6A receptor is indispensible for amino acid-induced secretion of GLP-1, we treated, with oral gavage, GPRC6A knock-out (KO) and wild-type (WT) littermate mice with GPRC6A ligands: L-arginine and L-ornithine, and assessed GLP-1 levels...... in circulation. We found that oral administration of both L-arginine and L-ornithine significantly increased total plasma GLP-1 levels to a similar level in GPRC6A KO and WT mice 15 minutes after gavage (both amino acids) and accumulated up to 60 minutes after gavage (L-arginine). Conversely, GLP-1 secretion...... at the 30 and 60 minute time points in the KO mice were attenuated and did not reach statistical significance. In summary, these data confirm that L-arginine is a potent GLP-1 secretagogue and show that the main effect occurs independently of GPRC6A. In addition, this is the first study to show that also L...

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 ...

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.

Radiological evaluation of long term complications of oral rehabilitations of thin ridges with titanium blade implants

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P. Diotallevi

2014-03-01

Full Text Available Aim: The aim of this study was to assess the sensitivity of orthopantomography (OPT in the diagnosis of long term complications in oral rehabilitations with blade implants. Materials and methods A total of 235 blade implants in 189 patients, inserted between 1988 and 2003, were retrospectively analyzed. The records consisted of a first OPT taken between January and December 2010, and a second one 12 months after. The evaluation of implant health considered: integrity of the blade, normal radiological representation of the bone around the implant, dense and cortical appearance of bone around the implant collar. The evaluation of radiological complications considered: implant fracture, bone resorption around the implant, recession of the bone around the implant collar. Results The sensitivity of the panoramic evaluation was equal to 100%. The complications detected were 5 cases of periimplantitis, 9 cases of bone pericervical bone recession and 3 cases of fracture of the implant body. In cases of pericervical bone resorption the following radiological check up 12 months after the first one showed the progression of the disease in 6 out of 9 cases, with irreversible implant failure. In subjects with a radiological pattern of implant health there were no complications in the subsequent check up after 12 months. In the subjects with complications the specificity was equal to 100%. Conclusion The radiographic evaluation by the means of OPT has shown high sensitivity in the diagnosis of long term complications of oral rehabilitations with blade implants and allows prompt therapeutic interventions. Radiological complications appeared mostly in the long term check ups and mainly consisted in recession of the bone around the neck or around the entire implant. More rarely implant fractures occurred, which, in the case of blades, sometimes were not associated with any clinical symptoms: therefore, postsurgical evaluation should not be separated from

Oral Supplementation with Beta-Hydroxy-Beta-Methylbutyrate, Arginine, and Glutamine Improves Lean Body Mass in Healthy Older Adults.

Science.gov (United States)

Ellis, Amy C; Hunter, Gary R; Goss, Amy M; Gower, Barbara A

2018-04-19

Oral intake of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine may ameliorate muscle loss by stimulating protein synthesis and decreasing protein degradation while simultaneously decreasing inflammation. Previous studies provide evidence for improvement in body composition with dietary supplementation of these ingredients among patients with muscle-wasting diseases. The objectives of this study were to examine the effects of this amino acid mixture on lean body mass, muscle volume, and physical function among healthy older adults. Thirty-one community-dwelling men and women, aged 65-89 years, were randomized to either two oral doses of the amino acid supplement (totaling 3 g HMB, 14 g arginine, 14 g glutamine) or placebo daily for six months. At baseline and month six, lean body mass was measured by air displacement plethysmography, dual-energy X-ray absorptiometry (DXA), and four-compartment model. Muscle volume of quadriceps was quantified by magnetic resonance imaging (MRI), and participants performed a battery of tests to assess physical function. As compared to the placebo group, the treatment group exhibited improvement in a timed stair climb (p =.016) as well as significant increases in lean body mass by all methods of assessment (p lean mass in the supplement group only (p =.035). However, no change was observed in MRI-derived quadriceps volume. Dietary supplementation with HMB, arginine, and glutamine improved total body lean mass among a small sample of healthy older adults. Further research is indicated to elucidate mechanisms of action and to determine whether supplementation may benefit frail elders. Registered under ClinicalTrials.gov identifier no. NCT01057082.

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

Long-term follow-up indicates unimpaired oral health-related quality of life for people having shortened dental arches

NARCIS (Netherlands)

Gerritsen, A.E.; Witter, D.J.; Creugers, N.H.J.

2017-01-01

OBJECTIVES: To assess and analyse OHRQoL of people with shortened dental arches (SDA) in a long-term cohort study. METHODS: All participants of a long-term cohort study on SDA who were still attending the university dental clinic and still had an SDA (SDA group) with 3-5 posterior occluding pairs

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

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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.

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.

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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

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 ...

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

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.

The Effect of Carbohydrates and Arginine on Arginine Metabolism by Excised Bean Leaves in the Dark

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Stewart, Cecil R.

1975-01-01

The effect of carbohydrate on arginine utilization by excised bean (Phaseolus vulgaris L. var. Tendergreen) leaves in the dark was studied by adding arginine to leaves differing in carbohydrate levels, and measuring the arginine content of the leaves at intervals. In nonstarved leaves, the arginine content decreased steadily after vacuum infiltration of 10 mm arginine and was essentially completely utilized by 36 hours after infiltration. In starved leaves, the arginine content did not decrease except for a brief period of about 4 hours after infiltration. The distribution of 14C after adding 14C-arginine to starved and nonstarved leaves indicated that the presence of carbohydrates in the leaves stimulates the utilization of arginine for protein synthesis and conversion to other amino acids, organic acids, and CO2 (catabolism). Adding sucrose along with arginine to starved leaves stimulated this utilization of arginine for both protein synthesis and catabolism. This effect of sugar on catabolism is different than results of similar studies done previously with proline. Increasing the concentration of added arginine greatly increased arginine catabolism but had a relatively small effect on utilization of arginine for protein synthesis. This result is the same as similar results from adding different concentrations of proline to excised leaves. PMID:16659159

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

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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.

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

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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.

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

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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.

Altered brain arginine metabolism in schizophrenia.

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Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

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

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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.

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

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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.

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

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Papp, Kim A; Krueger, James G; Feldman, Steven R; Langley, Richard G; Thaci, Diamant; Torii, Hideshi; Tyring, Stephen; Wolk, Robert; Gardner, Annie; Mebus, Charles; Tan, Huaming; Luo, Yingchun; Gupta, Pankaj; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. There was no dose comparison beyond week 52. Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol.

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Katharina Wylon

Full Text Available Vitamin D deficiency is frequent during the winter and occurs throughout the year in the elderly or patients suffering from autoimmune diseases. The objective of this study was to evaluate the pharmacokinetic properties of oral supplementation versus a single intramuscular injection of cholecalciferol in healthy individuals.Up to 8,000 I.U. oral cholecalciferol was administered daily for 84 days in a 4 week dose-escalation setting to vitamin D deficient individuals. In another cohort, a single intramuscular injection of 100,000 I.U. cholecalciferol was given. In both cohorts, individuals without vitamin D intake served as the comparison group. 25-hydroxyvitamin D (25(OHD concentrations were measured in all individuals at defined time points throughout the studies.The mean 25(OHD serum concentration increased significantly after oral cholecalciferol intake compared to the control group (day 28: 83.4 nmol/l and 42.5 nmol/l; day 56: 127.4 nmol/l and 37.3 nmol/l; day 84: 159.7 nmol/l and 30.0 nmol/l. In individuals receiving 100,000 I.U. cholecalciferol intramuscular, the mean 25(OHD serum concentration peaked after 4 weeks measuring 70.9 nmol/l compared to 32.7 nmol/l in the placebo group (p = 0.002. The increase of 25(OHD serum concentrations after 28 days was comparable between both routes of administration (p = 0.264.Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OHD concentrations.

Chinese L1 children's English L2 verb morphology over time: individual variation in long-term outcomes.

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Paradis, Johanne; Tulpar, Yasemin; Arppe, Antti

2016-05-01

This study examined accuracy in production and grammaticality judgements of verb morphology by eighteen Chinese-speaking children learning English as a second language (L2) followed longitudinally from four to six years of exposure to English, and who began to learn English at age 4;2. Children's growth in accuracy with verb morphology reached a plateau by six years, where 11/18 children did not display native-speaker levels of accuracy for one or more morphemes. Variation in children's accuracy with verb morphology was predicted by their English vocabulary size and verbal short-term memories primarily, and quality and quantity of English input at home secondarily. This study shows that even very young L2 learners might not all catch up to native speakers in this time frame and that non-age factors play a role in determining individual variation in child L2 learners' long-term outcomes with English morphology.

The subcellular compartmentalization of arginine metabolizing enzymes and their role in endothelial dysfunction

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Feng eChen

2013-07-01

Full Text Available The endothelial production of nitric oxide (NO mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle proliferation and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS through the conversion of its substrate, L-arginine to L-citrulline. Reduced access to L-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2 metabolize L-arginine to generate L-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of L-arginine. Indeed, supplemental L-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, L-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis suggesting additional mechanisms. The compartmentalization of intracellular L-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of L-arginine. Indeed the subcellular location of L-arginine metabolizing enzymes plays important functional roles. In endothelial cells, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localtion. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, ASL, co-localize with eNOS and facilitate NO release. This review highlights the importance of the subcellular location of eNOS and arginine transporting and metabolizing enzymes to NO release and cardiovascular disease.

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.

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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.

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

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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.

Role of long term antibiotics in chronic respiratory diseases.

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Suresh Babu, K; Kastelik, J; Morjaria, J B

2013-06-01

Antibiotics are commonly used in the management of respiratory disorders such as cystic fibrosis (CF), non-CF bronchiectasis, asthma and COPD. In those conditions long-term antibiotics can be delivered as nebulised aerosols or administered orally. In CF, nebulised colomycin or tobramycin improve lung function, reduce number of exacerbations and improve quality of life (QoL). Oral antibiotics, such as macrolides, have acquired wide use not only as anti-microbial agents but also due to their anti-inflammatory and pro-kinetic properties. In CF, macrolides such as azithromycin have been shown to improve the lung function and reduce frequency of infective exacerbations. Similarly macrolides have been shown to have some benefits in COPD including reduction in a number of exacerbations. In asthma, macrolides have been reported to improve some subjective parameters, bronchial hyperresponsiveness and airway inflammation; however have no benefits on lung function or overall asthma control. Macrolides have also been used with beneficial effects in less common disorders such as diffuse panbronchiolitis or post-transplant bronchiolitis obliterans syndrome. In this review we describe our current knowledge the use of long-term antibiotics in conditions such as CF, non-CF bronchiectasis, asthma and COPD together with up-to-date clinical and scientific evidence to support our understanding of the use of antibiotics in those conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

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Workman, Joanna L; Weber, Michael D; Nelson, Randy J

2011-09-30

Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

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

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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

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

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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.

Long-term improvements in oral communication skills and quality of peer relations in children with cochlear implants: parental testimony.

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Bat-Chava, Y; Martin, D; Imperatore, L

2014-11-01

Few research studies have examined longitudinal improvements in oral communication skills and quality of peer relationships of children with implants. Moreover, although the emerging literature suggests that improvement in social functioning follows improvement in oral communication, it is still unknown what factors enhance or impede the relations between these constructs. Based on parent interviews, the current study examined the long-term improvements in speech and oral language skills and relationships with hearing peers in 19 implanted children. Results demonstrate that on average, children continue to improve in oral communication skills and quality of peer relationships even years after implantation, especially those with initial poorer skills. While oral communication ability and quality of peer relationships are strongly associated at each time point, gains in these two variables are associated only for some of the children. Other factors, including self-confidence and peer acceptance, seem to moderate this relationship. Qualitative data are presented to illustrate these relations among variables and to assist in theory building. The results highlight the need for more specific examination of various developmental periods in combination with the progress of oral communication and peer relationships among children with implants. © 2013 John Wiley & Sons Ltd.

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

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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...

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

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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.

Role of nitric oxide in long-term potentiation of the rat medial vestibular nuclei.

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Grassi, S; Pettorossi, V E

2000-01-01

In rat brainstem slices, we investigated the role of nitric oxide in long-term potentiation induced in the ventral portion of the medial vestibular nuclei by high-frequency stimulation of the primary vestibular afferents. The nitric oxide scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide ] and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester were administered before and after induction of potentiation. Both drugs completely prevented long-term potentiation, whereas they did not impede the potentiation build-up, or affect the already established potentiation. These results demonstrate that the induction, but not the maintenance of vestibular long-term potentiation, depends on the synthesis and release into the extracellular medium of nitric oxide. In addition, we analysed the effect of the nitric oxide donor sodium nitroprusside on vestibular responses. Sodium nitroprusside induced long-term potentiation, as evidenced through the field potential enhancement and unit peak latency decrease. This potentiation was impeded by D, L-2-amino-5-phosphonopentanoic acid, and was reduced under blockade of synaptosomal platelet-activating factor receptors by ginkgolide B and group I metabotropic glutamate receptors by (R,S)-1-aminoindan-1, 5-dicarboxylic acid. When reduced, potentiation fully developed following the washout of antagonist, demonstrating an involvement of platelet-activating factor and group I metabotropic glutamate receptors in its full development. Potentiation induced by sodium nitroprusside was also associated with a decrease in the paired-pulse facilitation ratio, which persisted under ginkgolide B, indicating that nitric oxide increases glutamate release independently of platelet-activating factor-mediated presynaptic events. We suggest that nitric oxide, released after the activation of N-methyl-D-aspartate receptors, acts as a retrograde messenger leading to an enhancement of glutamate release to a

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.

Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.

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Kina-Tanada, Mika; Sakanashi, Mayuko; Tanimoto, Akihide; Kaname, Tadashi; Matsuzaki, Toshihiro; Noguchi, Katsuhiko; Uchida, Taro; Nakasone, Junko; Kozuka, Chisayo; Ishida, Masayoshi; Kubota, Haruaki; Taira, Yuji; Totsuka, Yuichi; Kina, Shin-Ichiro; Sunakawa, Hajime; Omura, Junichi; Satoh, Kimio; Shimokawa, Hiroaki; Yanagihara, Nobuyuki; Maeda, Shiro; Ohya, Yusuke; Matsushita, Masayuki; Masuzaki, Hiroaki; Arasaki, Akira; Tsutsui, Masato

2017-06-01

Nitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.

Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy

International Nuclear Information System (INIS)

Murayama, Masanori; Yasuda, Keigo; Minamori, Yoshiaki; Mercado-Asis, L.B.; Morita, Hiroyuki; Miura, Kiyoshi; Yamakita, Noriyoshi.

1994-01-01

Subtotal adrenalectomy was given to 10 adult patients with Cushing's disease, concurrently with or following therapeutic regimen by long term reserpine administration and pituitary irradiation. In the present study, we describe long term follow-up results. Two patients died after the operation due to acute adrenal crisis and pneumonia, respectively. The other 8 patients achieved clinical and biochemical remissions and were followed for long term. Three patients relapsed 9, 14 or 17 years after achieving remission, two patients developed hypopituitarism 12 or 20 years after and one died of cerebral vascular accident at 64 years, 5 years after the remission. The remaining 2 patients maintained remission for 10 or 18 years, respectively. During the remission periods of 0.5 to 20 years with a mean of 10.1±6.7 years, 6 of 7 patients examined by 1 mg overnight dexamethasone test showed normal suppressibility of plasma cortisol. Provocative tests of plasma GH by 1-arginine infusion and/or insulin-induced hypoglycemia were performed in 6 patients in the early remission period. All of 5 patients in the arginine infusion test and 3 of 5 in the insulin-induced hypoglycemia test showed normal responses. Furthermore, to facilitate prediction of long term response or failure to our therapeutic regimen, long term reserpine administration and pituitary irradiation, pretreatment clinical and biochemical characteristics were analyzed retrospectively in 3 divided groups; the present 10 patients treated with reserpine and pituitary irradiation followed by subtotal adrenalectomy, 11 patients achieving long term remission treated by our regimen alone, and 7 patients failed with our regimen alone. There were no significant factors predictive of response to our regimen. (author)

Long-term L-Triiodothyronine (T3) treatment in stable systolic heart failure patients

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Holmager, Pernille; Schmidt, Ulla; Mark, Peter

2015-01-01

%, range: 37-52 and serum T3 levels 1·4 nmol/l (0·9-1·6). The T3 dose was 20 μg per day (10-40). TSH levels did not change between groups, whereas serum T3 levels increased in the active arm. Cardiac function as measured by LVEF, end-diastolic and end-systolic volumes and cardiac output did not change...... during T3-treatment and neither did the neurohormonal profile. There were no side-effects in terms of cardiac arrhythmias and no change in resting heart rate. CONCLUSIONS: This study does not support the hypothesis that oral T3 treatment might be beneficial to patients with chronic, stable systolic HF...

Short and long-term soy diet vs. casein protects liver steatosis independent of the arginine content

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Non-alcoholic fatty liver disease (NAFLD), the major cause of abnormal liver function, is often associated with obesity. Arginine (ARG) plays a role in modulating body weight/fat, but there are limited data as to the role that ARG may play in soy protein’s ability to protect from liver steatosis. Th...

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

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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

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

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Stühlinger, Markus C; Stanger, Olaf

2005-02-01

Hyperhomocyst(e)inemia is associated with an increased risk for atherosclerotic disease and venous thromboembolism. The impact of elevated plasma homocysteine levels seems to be clinically relevant, since the total cardiovascular risk of hyperhomocyst(e)inemia is comparable to the risk associated with hyperlipidemia or smoking. There is substantial evidence for impairment of endothelial function in human and animal models of atherosclerosis, occurring even before development of overt plaques. Interestingly endothelial dysfunction appears to be a sensitive indicator of the process of atherosclerotic lesion development and predicts future vascular events. NO is the most potent endogenous vasodilator known. It is released by the endothelium, and reduced NO bioavailability is responsible for impaired endothelium-dependent vasorelaxation in hyperhomocyst(e)inemia and other metabolic disorders associated with vascular disease. Substances leading to impaired endothelial function as a consequence of reduced NO generation are endogenous NO synthase inhibitors such as ADMA. Indeed there is accumulating evidence from animal and human studies that ADMA, endothelial function and homocyst(e)ine might be closely interrelated. Specifically elevations of ADMA associated with impaired endothelium-dependent relaxation were found in chronic hyperhomocyst(e)inemia, as well as after acute elevation of plasma homocyst(e)ine following oral methionine intake. The postulated mechanisms for ADMA accumulation are increased methylation of arginine residues within proteins, as well as reduced metabolism of ADMA by the enzyme DDAH, but they still need to be confirmed to be operative in vivo. Hyperhomocyst(e)inemia, as well as subsequent endothelial dysfunction can be successfully treated by application of folate and B vitamins. Since ADMA seems to play a central role in homocyst(e)ine-induced endothelial dysfunction, another way of preventing vascular disease in patients with elevated homocyst

Arginine affects appetite via nitric oxide in ducks.

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Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

2014-08-01

The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. © Poultry Science Association Inc.

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

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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.

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.

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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

Modulators of arginine metabolism support cancer immunosurveillance

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Freschi Massimo

2009-01-01

Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

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

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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

Long-Term Endocrine Outcomes Following Endoscopic Endonasal Transsphenoidal Surgery for Acromegaly and Associated Prognostic Factors.

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Babu, Harish; Ortega, Alicia; Nuno, Miriam; Dehghan, Aaron; Schweitzer, Aaron; Bonert, H Vivien; Carmichael, John D; Cooper, Odelia; Melmed, Shlomo; Mamelak, Adam N

2017-08-01

Long-term remission rates from endoscopic transsphenoidal surgery for acromegaly and their relationship to prognostic indicators of disease aggressiveness are not well documented. To investigate long-term remission rates in patients with acromegaly after endoscopic transsphenoidal surgery, and correlate this with molecular and radiographic markers of disease aggressiveness. We identified all patients undergoing endoscopic transsphenoidal surgery for acromegaly from 2005 to 2013 at Cedars-Sinai Pituitary Center. Hormonal remission was established by normal insulin-like growth factor (IGF)-1, basal serum growth hormone <2.5 ng/mL, and growth hormone suppression to <1 ng/mL following oral glucose tolerance test. Oral glucose tolerance test was performed at 3 months after surgery, and then as indicated. IGF-1 was measured at 3 months and then at least annually. We evaluated tumor granularity, nuclear expression of p21, Ki67 index, and extent of cavernous sinus invasion, and correlated these with remission status. Fifty-eight patients that underwent surgery had follow-up from 38 to 98 months (mean 64 ± 32.2 months). There were 21 microadenomas and 37 macroadenomas. Three months after surgery 40 of 58 patients (69%) were in biochemical remission. Four additional patients were in remission at 6 months after surgery, and 1 patient had recurrence within the first year after surgery. At last follow-up, 43 of 44 (74.1%) of patients remained in remission. Cavernous sinus invasion by tumor predicted failure to achieve remission. Prognostic markers of disease aggressiveness other than cavernous sinus invasion did not correlate with surgical outcome. Long-term remission after surgery alone was achieved in 74% of patients, indicating long-term efficacy of endoscopic surgery. Copyright © 2017 by the Congress of Neurological Surgeons

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

DEFF Research Database (Denmark)

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

2012-01-01

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

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.

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

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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.

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)

Verbal short-term memory span in children: long-term modality dependent effects of intrauterine growth restriction.

Science.gov (United States)

Geva, R; Eshel, R; Leitner, Y; Fattal-Valevski, A; Harel, S

2008-12-01

Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). We found IUGR-related specific auditory-oral STM deficits (p long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.

Marked elevation in plasma trimethylamine-N-oxide (TMAO in patients with mitochondrial disorders treated with oral l-carnitine

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H.D. Vallance

2018-06-01

Full Text Available Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO, is an independent and dose-dependent risk factor for cardiovascular disease (CVD. Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed plasma TMAO levels in patients with mitochondrial disease with and without oral l-carnitine supplementation. Nine subjects were recruited and completed the study. Eight out of 9 subjects at baseline had plasma TMAO concentrations <97.5th percentile (<15.5 μM. One subject with stage 3 renal disease, had marked elevation in plasma TMAO (pre 33.98 μm versus post 101.6 μm. Following at least 3 months of l-carnitine supplementation (1000 mg per day, plasma TMAO levels were markedly increased in 7out of 9 subjects; overall, plasma TMAO significantly increased 11.8-fold (p < 0.001 from a baseline median level of 3.54 μm (interquartile range (IQR 2.55–8.72 to 43.26 (IQR 23.99–56.04 post supplementation. The results of this study demonstrate that chronic oral l-carnitine supplementation markedly increases plasma TMAO levels in subjects with mitochondrial disorders. Further studies to evaluate both the efficacy and long term safety of oral l-carnitine supplementation for the treatment of mitochondrial disorders are warranted. Keywords: l-carnitine, Trimethylamine N-oxide, Mitochondrial disorders

Long-term outcomes of oral rehabilitation with dental implants in HIV-positive patients: A retrospective case series.

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Gay-Escoda, C; Pérez-Álvarez, D; Camps-Font, O; Figueiredo, R

2016-05-01

The existing information on oral rehabilitations with dental implants in VIH-positive patients is scarce and of poor quality. Moreover, no long-term follow-up studies are available. Hence, the aims of this study were to describe the long-term survival and success rates of dental implants in a group of HIV-positive patients and to identify the most common postoperative complications, including peri-implant diseases. A retrospective case series of HIV-positive subjects treated with dental implants at the School of Dentistry of the University of Barcelona (Spain) was studied. Several clinical parameters were registered, including CD4 cell count, viral load and surgical complications. Additionally, the patients were assessed for implant survival and success rates and for the prevalence of peri-implant diseases. A descriptive statistical analysis of the data was performed. Nine participants (57 implants) were included. The patients' median age was 42 years (IQR=13.5 years). The implant survival and success rates were 98.3% and 68.4%, respectively, with a mean follow-up of 77.5 months (SD=16.1 months). The patient-based prevalence of peri-implant mucositis and peri-implantitis were 22.2% and 44.4% respectively at the last appointment. Patients that attended regular periodontal maintenance visits had significantly less mean bone loss than non-compliant patients (1.3 mm and 3.9 mm respectively). Oral rehabilitation with dental implants in HIV-positive patients seems to provide satisfactory results. In order to reduce the considerably high prevalence of peri-implant diseases, strict maintenance programmes must be implemented.

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

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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.

Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.

Science.gov (United States)

Duffy, S J; Keaney , J F; Holbrook, M; Gokce, N; Swerdloff, P L; Frei, B; Vita, J A

2001-07-10

Epidemiological studies suggest that tea consumption decreases cardiovascular risk, but the mechanisms of benefit remain undefined. Endothelial dysfunction has been associated with coronary artery disease and increased oxidative stress. Some antioxidants have been shown to reverse endothelial dysfunction, and tea contains antioxidant flavonoids. Methods and Results-- To test the hypothesis that tea consumption will reverse endothelial dysfunction, we randomized 66 patients with proven coronary artery disease to consume black tea and water in a crossover design. Short-term effects were examined 2 hours after consumption of 450 mL tea or water. Long-term effects were examined after consumption of 900 mL tea or water daily for 4 weeks. Vasomotor function of the brachial artery was examined at baseline and after each intervention with vascular ultrasound. Fifty patients completed the protocol and had technically suitable ultrasound measurements. Both short- and long-term tea consumption improved endothelium- dependent flow-mediated dilation of the brachial artery, whereas consumption of water had no effect (Peffect on endothelium-independent nitroglycerin-induced dilation. An equivalent oral dose of caffeine (200 mg) had no short-term effect on flow-mediated dilation. Plasma flavonoids increased after short- and long-term tea consumption. Short- and long-term black tea consumption reverses endothelial vasomotor dysfunction in patients with coronary artery disease. This finding may partly explain the association between tea intake and decreased cardiovascular disease events.

Long-term consumption of aspartame and brain antioxidant defense status.

Science.gov (United States)

Abhilash, M; Sauganth Paul, M V; Varghese, Mathews V; Nair, R Harikumaran

2013-04-01

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Long-term stability of influenza vaccine in a dissolving microneedle patch.

Science.gov (United States)

Mistilis, Matthew J; Joyce, Jessica C; Esser, E Stein; Skountzou, Ioanna; Compans, Richard W; Bommarius, Andreas S; Prausnitz, Mark R

2017-04-01

This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.

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.

Effects of Long-term Use of Polyphenols on the Absorption and Tissue Distribution of Orally Administered Metformin and Atenolol in Rats

Directory of Open Access Journals (Sweden)

Saad Abdulrahman Hussain

2013-06-01

Full Text Available Aim: To evaluate the effect of long-term use of silibinin, epigallocatechin (ECGC, quercetin and rutin on the absorption and tissue distribution of metformin and atenolol. Materials and Methods: Thirty male rats were used, allocated into 5 groups and treated as follow: 1st group treated with olive oil and served as control; the other 4 groups were treated with either silibinin, EPGC, quercetin or rutin, administered orally as oily solutions for 30 days. At day 30, a 300mg/kg metformin and 50mg/kg atenolol were administered orally; 3.0 hrs later, the animals were sacrificed and blood samples, tissues of brain, kidney and liver were obtained for evaluation of the drugs level. Results: The polyphenols increased both serum and tissue levels of metformin compared with controls. This effect was relatively varied according to the structural differences among flavonoids. Conclusion: Long-term use of supraphysiological doses of flavonoids increase absorption of Zn, Cu and Fe and their tissue availability in brain, kidney and liver; this effect seems to be different with variations in structural features. [J Intercult Ethnopharmacol 2013; 2(3.000: 147-154

[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.

The ArcD1 and ArcD2 arginine/ornithine exchangers encoded in the arginine deiminase (ADI) pathway gene cluster of Lactococcus lactis

NARCIS (Netherlands)

Noens, Elke E E; Kaczmarek, Michał B; Żygo, Monika; Lolkema, Juke S

2015-01-01

The arginine deiminase pathway (ADI) gene cluster in Lactococcus lactis contains two copies of a gene encoding an L-arginine/L-ornithine exchanger, the arcD1 and arcD2 genes. The physiological function of ArcD1 and ArcD2 was studied by deleting the two genes. Deletion of arcD1 resulted in loss of

Effect of zinc supplementation of pregnant rats on short-term and long-term memory of their offspring

International Nuclear Information System (INIS)

Ali, M.A.; Ghotbeddin, Z.; Parham, G.H.

2007-01-01

To see the dose dependent effects of zinc chloride on the short-term and long-term memory in a shuttle box (rats). Six pair adult wistar rats were taken for this experiment. One group of pregnant rats received a daily oral dose of 20 mg/kg Zn as zinc chloride and the remaining groups received a daily oral dose of (30, 50, 70,100 mg/kg) zinc chloride for two weeks by gavage. One month after birth, a shuttle box was used to test short-term and long-term memory. Two criteria were considered to behavioral test, including latency in entering dark chamber and time spent in the dark chamber. This experiment showed that oral administration of ZnCl/sub 2/ with (20, 30, 50 mg/kg/day) doses after 2 weeks at the stage of pregnancy, can improve the working memory of their offspring (p<0.05). Where as ZnCl/sub 2/ with 30 mg/kg/day dose has been more effective than other doses (p<0.001). But rat which received ZnCl/sub 2/ with 100 mg/kg/day at the stage of pregnancy, has shown significant impairment in working (short-term) memory of their offspring (p<0.05) and there was no significant difference in reference (long-term) memory 3 for any of groups. This study has demonstrated that zinc chloride consumption with 30 mg/kg/day dose for two weeks at the stage of pregnancy in rats, has positive effect on short-term memory on their offspring. But consumption of enhanced zinc 100 mg/kg/day in pregnant rats can cause short-term memory impairment. On the other hand, zinc supplementation such as zinc chloride has no effect on long-term memory. (author)

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.

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.

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.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

Science.gov (United States)

Olivares, J M; Rodriguez-Morales, A; Diels, J; Povey, M; Jacobs, A; Zhao, Z; Lam, A; Villalobos Vega, J C; Cuéllar, J Alonso; de Castro, F J Alberca; Quintero, C Morillo-Velarde; Martíin, J F Román; Domínguez, P Tabares; Ojeda, J L Prados; Cortés, S Sanz; Cala, F I Mata; Marín, C Gutiérrez; Castro, L Moyano; Duaso, M A Haza; Albarracín, J Requena; Vergara, G Narbona; Benítez, A Fernández; Cleries, F Mayoral; Pérez-Brian, J M García-Herrera; Aragón, A Bordallo; Navarro, J C Rodríguez; Biedma, J A Algarra; de Pedro, R Bravo; González, J F Delgado; López, M E Jaén; Moreno, H Díaz; López, J A Soto; Rodríguez, E Ojeda; de Hoyos, C Martínez; Sacristán, M Pardilla; Martín, M D Molina; Ballesteros, E Martín; Rodríguez, P A Sopelana; Menéndez, L Fernández; Rivas, R Santos; del Pino Cuadrado, P; Lauffer, J Correas; Solano, J J Rodríguez; Martínez, J M Fernández; Solano, F García; Rodríguez, P García-Lamberde; Rodríguez, J A Romero; Cano, T Rodríguez; Fortacin, M Ducaju; Lobeiras, J M Blanco; Sampedro, J M Piñeiro; Bravo, A Pérez; Pellicer, A Fernández; López, M D Alonso; Liste, J Fraga; Fernández, M Riobo; Losada, A Casas; Mendez, R Vazquez-Noguerol; Romero, S Agra; Blanco, J J Blanco; Bonaselt, I Tortajada; Mahia, M C García; del Valle, E Ferrer Gómez; Yañez, P Quiroga; Camarasa, M Gelabert; Alonso, J A Barbado; Mendez, G Florez; Feliz, F Doce; Lamela, M A López; Piñero, M Vega; Alvarado, P Fuentes; Gómez, I López; Martín, P Fadon; Gómez, J L Santos; López, A García; Jiménez, A Rodríguez; Nafs, A Escudero; Barquero, N Casas; Ortiz, R Fernández-Villamor; Noguera, J L Velez; Carrasco, P Ruiz; Muñoz, J Martín; Palma, M Masegoza; Hortelano, C Marín; Bonome, L Sánchez; Sevilla, J Sánchez; Juan, J M Mongil San; Ramos, J M García; Muñoz, J L Vallejo; Guisasola, J Elorza; Vazquez, L Santamaria; Guerras, F Campo; Nebot, F J Arrufat; Fernández, F J Baron; Nicolau, A L Palomo; Subirats, R Catala; Kidias, M Messays; Navarro, V Fabregat; García, B Frades; del Rosal, F Mejias; de Vicente Muñoz, T; Ballester, J Año; Lieb, P Malabia; Martel, A Delgado; Bea, E Roca; Joaquim, I Grau; Enjuanes, F Boatas; Piñol, M Bañuelos; Carbonell, E Fontova I; Muñoz, R Martín; Giribets, C Argila; Sans, L Albages; Blanco, A Serrano; Felipe, M Arcega; Muñoz, P González; Villanueva, A Pons; Arroyo, M Bernardo; Borri, R Coronas; Fallada, S Miret; Merola, M Celma; Rodon, E Parellada; Palmes, J R Pigem; Martínez, E Pérez; Catala, J Matarredona; Coca, A Sandoval; Ferrandiz, F Pascual; Paya, E Ferrandiz; Caballero, G Iturri; Bonet, A Franco; Figueras, J Fluvia; Pagador, P Moreno; Garibo, M Medina; Camo, V Pérez; Carrillo, C Sanz; Valero, C Pelegrin; Rebollo, F J Caro; García Campayo, J; Sala Ayma, J M Sala; Roig, M Martínez; de Uña Mateos, M A; Bertolin, R García; García, A Martín; Mazo, F Jiménez; Velasco, J L Galvez; Pérez, L Santa Maria; Casado, C Jiménez; Barba, J J Mancheño; Diaz, M Conde; Rubio, J P Alcon; Mandoli, A Soler; Herrero, A Uson; Martínez, A Rodríguez; Serrano, P Salgado; Rodríguez, E Nieto; Montesinos, J Segui; Macia, J Ferragud; Mateos Marcos, A Mateos; Soto, J V Pérez-Fuster; Dumont, M Verdaguer; Pagan, J Parra; Martínez, V Balanza; Santiuste de Pablos, M; Delgado, C Espinosa; Quiles, M D Martínez; López, F J Manzanera; Navarro, P Pozo; Torres, A Micol; Ingles, F J Martínez; Arias-Camison, J M Salmeron; Manzano, J C López; Peña, R Villanueva; Guitarte, G Petersen; Fontecilla, H Blasco; Romero, J Barjau; Gil, R Sanz; Lozano, J Marín; Adanez, L Donaire; Zarranz Herrera-Oria, I; Jiménez, J Pérez; Vaz, F Carrato; García, O Sanz; Anton, C Contreras; Casula, R Reixach; Hernandez, M C Natividad; Escabias, F Teba; Torresano, J Rodríguez; Pérez-Villamil, A Huidobro; Estevez, L; Figuero, M Aragües; Muñoz de Morales, A; Calvin, J L Rodríguez; Criado, M Delgado; Rodríguez, V Molina; Ambrosolio, E Balbo; Madera, P M Holgado; Alfaro, G Ponce; Vidal, M M Rojas; Valtuille, A García; Ruiz, O; Cabornero, G Lucas; Echevarria Martínez de Bujo, M; Mallen, M J Maicas; Puigros, J Santandreu; Martorell, A Liñana; Forteza, A Clar; Arrebola, E Rodríguez; Rodríguez de la Torre, M; Saiz, C G Anton; Bardolet I Casas, C; Linde, E Rodríguez; De Arce Cordon, R; Molina, E M Padial; Carazo, F J Ruiz; Romero, J J Muro; Cano, D Vico; Dorado, M Soria; Velazquez, S Campos; Sánchez, A J Rodríguez; Leon, S Ocio; Sánchez, K Pachas; Benitez, M Henry; Zugarramurai, A Intxausti; Contreras, M A; De la Varga González, M; Marín, P Barreiro; Robina, F Gómez; García, M Sánchez; Pérez, F J Otero; Bros, P Cubero; Gómez, A Carrillo; de Dios Molina Martín, J; Perera, J L Carrasco; Averbach, M C; Perera, J L Carrasco; Palancares, E Goenaga; Gallego de Dios, M T; Rojo, C Fernández; Iglesias, S Sánchez; Merino, M I Rubio; Mestre, N Prieto; Urdaniz, A Pérez; Sánchez, J M Martínez; Seco, R Gordo; Muñoz, J Franco; Agut, M Mateos; Lozano, M L Blanco; Herguedas, F Martín; Pena, A Torcal; García, J Vicente; Martínez, A Varona; Sanz Granado, O Sanz; Fernández, M A Medina; Canseco, J M Moran; López, P A Megia; Martín, M A Franco; Barrio, J A Espina; Ubago, J Giner; Bennassar, M Roca; Díez, J M Olivares; Fleta, J L Hernandez; Fortes, F Porras; López, C Arango; Medina, O; Alvarez, D Figuera; Roca, J M Peña; Valladolid, G Rubio; Tavera, J A Furquet; García-Castrillon Sales, J A; Llordes, I Batalla; Melgarejo, C Anchuistegui; Cañas de la Paz, F; Callol, V Vallés; García, M Bousoño; García, J Bobes; Leal, F J Vaz; Corrales, E Cáceres; Iglesias, E Sánchez; Gómez, M A Carreiras; Serrano, G García; Chillarón, E G Román; Aguado, F J Samino; Castillo, J J Molina; González, A González; Vázquez, J Gallardo; Peralvarez, M Bolivar; Diaz, M Rios; Mesa, M Ybarzabal; Artiles, F J Acosta; Chao, M Ajoy; Mesa, M Ybarzabal; del Rosario Santana, P; Escudero, M A García; Berenguer, M Molla; Llacer, J M Bonete; Berna, J A Juan; Ortiz, J Barragán; Pardell, L Tost; Hernández-Alvarez de Sotomayor, C; Méndez, M R Cejas; Garate, R Cabrera; Múgica, B Díaz; González, M Caballero; Domingo, J Pujol; Navarro, C Sáez; Vera, G Selva; Cuquerella, M A; Monzo, J Lonjedo; Boada, P Cervera; Pérez, M F Martín; Parrado, E Carrasco; Sánchez, J J Yañez; Fernández, J Calvo

2009-06-01

The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

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

Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder

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Maha Mourad

2016-11-01

Full Text Available Urea cycle disorders (UCDs are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD. OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes, cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H. Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers.

Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

Science.gov (United States)

Lockitch, G; Puterman, M; Godolphin, W; Sheps, S; Tingle, A J; Quigley, G

1989-05-01

To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

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)

Effect of Long Term Oral Warfarin Sodium Treatment on Bone Mineral Density Scores and Spinal Sagittal Alignment

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Kamil Eyvazov

2016-04-01

Full Text Available Objective: The aim of this study was to investigate the effect of long term oral warfarin sodium treatment on bone mineral density (BMD and spinal sagittal alignment. Materials and Methods: Sixty four participants were enrolled for this retrospective study. Participants were divided into two groups-participants who had taken warfarin sodium for at least two years (n=33 and participants who had never taken warfarin sodium (n=31. All of the individuals were evaluated at the same center. Dual X-ray absorptiometry (DXA was used for measuring BMD. Whole spine x-rays were obtained for sagittal assessment and the following parameters were measured: Cervical lordosis, thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope and sagittal vertical axis (SVA. Results: The mean BMD value was significantly higher in participants who had not taken warfarin sodium compared to participants who had taken warfarin sodium. The differences between the average values were 0.1552 g/cm2 in BMD; 2.1 in T scores; 1.4 in Z scores. On the radiological evaluation of the spine, cervical lordosis was 7.1 degrees lower, lumbar lordosis was 4.7 degrees lower and thoracic kyphosis was 5.3 degrees higher in the patients using drug. C7 plumb line was interchanged forward in the patients using drug. Conclusions: This study shows that warfarin sodium use worsens bone quality in the lumbar region and does not affect bone quality in the femoral region. Furthermore, warfarin sodium use also reduces physiological lordosis and enhances thoracic kyphosis. Consequences of these changes are the likely cause of sagittal spinal anterior imbalance. Long-term oral warfarin sodium use affect bone mineral density and spinal alignment. Our conclusion about giving clear message and show exactly mechanism we need prospective randomized multicentre studies in future. We strongly believe this study will be pioneer for future researches.

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome.

Science.gov (United States)

Warinner, Christina; Speller, Camilla; Collins, Matthew J

2015-01-19

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.

A new era in palaeomicrobiology: prospects for ancient dental calculus as a long-term record of the human oral microbiome

Science.gov (United States)

Warinner, Christina; Speller, Camilla; Collins, Matthew J.

2015-01-01

The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes. PMID:25487328

[Oral health hygiene education programme for nursing personnel to improve oral health of residents in long-term care facilities 2010 in Frankfurt/Main, Germany].

Science.gov (United States)

Czarkowski, G; Allroggen, S; Köster-Schmidt, A; Bausback-Schomakers, S; Frank, M; Heudorf, U

2013-06-01

demonstrated, significant for plaque index, cleanliness of the tongue and denture hygiene index. The positive assessment of the nursing personnel as well as the positive effects on oral hygiene in the residents are in agreement with the results of many other studies in many countries. Therefore, these education programmes will be continued in the long-term care facilities in Frankfurt/Main, Germany.· © Georg Thieme Verlag KG Stuttgart · New York.

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.

Factors Affecting Grammatical and Lexical Complexity of Long-Term L2 Speakers' Oral Proficiency

Science.gov (United States)

Lahmann, Cornelia; Steinkrauss, Rasmus; Schmid, Monika S.

2016-01-01

There remains considerable disagreement about which factors drive second language (L2) ultimate attainment. Age of onset (AO) appears to be a robust factor, lending support to theories of maturational constraints on L2 acquisition. The present study is an investigation of factors that influence grammatical and lexical complexity at the stage of L2…

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

Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy

International Nuclear Information System (INIS)

Simon, Thorsten; Hero, Barbara; Faldum, Andreas; Handgretinger, Rupert; Schrappe, Martin; Klingebiel, Thomas; Berthold, Frank

2011-01-01

The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective

Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy

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Schrappe Martin

2011-01-01

Full Text Available Abstract Background The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide. In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months. Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69 served as controls. Results The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098. In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038. The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4% compared to NB90 MT (34 ± 5%, p = 0.026 and to no consolidation (35 ± 6%, p = 0.019. Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.

Functional and immunohistochemical evaluation of porcine neonatal islet-like cell clusters

DEFF Research Database (Denmark)

Nielsen, T B; Yderstraede, K B; Schrøder, H D

2003-01-01

Porcine neonatal islet-like cell clusters (NICCs) may be an attractive source of insulin-producing tissue for xenotransplantation in type I diabetic patients. We examined the functional and immunohistochemical outcome of the islet grafts in vitro during long-term culture and in vivo after...... transplantation to athymic nude mice. On average we obtained 29,000 NICCs from each pancreas. In a perifusion system, NICCs responded poorly to a glucose challenge alone, but 10 mmol/L arginine elicited a fourfold increase in insulin secretion and 16.7 mmol/L glucose + 10 mmol/L arginine caused a sevenfold...... co-stained for proliferation. However no co-staining was observed between insulin- and glucagon-positive cells or between hormone-and CK-positive cells. Following transplantation of 2000 NICCs under the renal capsule of diabetic nude mice, BG levels were normalized within an average of 13 weeks. Oral...

Effect of iron, taurine and arginine on rat hepatic fibrosis

International Nuclear Information System (INIS)

Song Liangwen; Wang Dewen; Cui Xuemei

1997-01-01

Objective: The promotion role of iron on pathogenesis of hepatic fibrosis and the protective role of taurine and L-arginine against hepatic fibrosis were studied. Method: The model of rat radiation hepatic fibrosis was used. Experimental rats were divided into 0 Gy, 30 Gy, 30 Gy + iron, 30 Gy + taurine and 30 Gy + L-arginine groups. Serum iron, liver tissue hydroxyproline (Hyp) and malondialdehyde (MDA) were measured one and three months respectively after irradiation of hepatic tissue, production and distribution characteristics of hepatic tissue type I and III collagen were observed with a polarizing microscope. Results: Administration of iron agent could significantly increase hepatic tissue MDA content and serum iron concentration, one month after irradiation, hepatic tissue Hyp in 30 Gy + iron group began to increase, and collagen in hepatic tissue obviously increased. Taurine and L-arginine could reduce serum iron concentration and decrease production of hepatic fissure Hyp. Conclusion: Exogenous iron agent could promote early development of radiation hepatic fibrosis; taurine and arginine could diminish pathologic alteration of hepatic fibrosis to a certain extent

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.

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.

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

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...

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

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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.

Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes

NARCIS (Netherlands)

I.M. Garrelds (Ingrid); G.R. Elliott (G.); F.J. Zijlstra (Freek); I.L. Bonta

1994-01-01

textabstractThe effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids front in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A

Long-term effects of intermittent oral alphacalcidol, calcium carbonate and low-calcium dialysis (1.25 mmol L-1) on secondary hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis

DEFF Research Database (Denmark)

Brandi, L; Nielsen, P K; Bro, S

1998-01-01

of the secondary hyperparathyroidism was seen. CONCLUSIONS: A calcium concentration of 1.25 mmol L-1 in the CAPD dialysate made it possible to reduce the amount of aluminium-containing phosphate binder, to increase the doses of CaCO3 and to use pulse oral 1 alpha(OH)D3 without causing severe hyper...... L-1 to 1.25 mmol L-1. Increasing doses of oral 1 alpha(OH)D3 were then administered under careful control of p-ionized calcium (p-Ca2+) and p-inorganic phosphate (p-P1). Blood samples were obtained every 2-4 weeks for 52 weeks. PET was performed using standard dialysis fluid and 1 week later using...... low-calcium dialysis fluid after a preceding overnight dwell. Two litres of glucose 22.7 mg mL-1 were used. MAIN OUTCOME MEASURES: Intact parathyroid hormone (PTH), p-Ca2+, p-P1, doses of CaCO3, doses of 1 alpha(OH)D3, peritoneal mass transfer for calcium, inorganic phosphate, magnesium, lactate...

Results on long-term performances and laboratory tests of the L3 RPC system at LEP

CERN Document Server

Alviggi, M G; Conventi, F; De Asmundis, R; Della Pietra, M; Della Volpe, D; Patricelli, S; Paolucci, P; Piccolo, D; Sciacca, C; Sekhniaidze, G

2003-01-01

The RPC detectors in the L3 experiment at LEP work as a trigger system for the Forward-Backward Muon Spectrometer. It consists of 192 bi-gap RPCs working in streamer mode. We monitored the behaviour of the system over seven years of data taking at LEP. To investigate the ageing of the RPCs after this long-term operation, we report the main results obtained from 1994 to 2000, together with the results of tests performed on some RPC chambers in our test site in Napoli with cosmic rays after the dismantling of L3.

Factors Affecting Grammatical and Lexical Complexity of Long-Term L2 Speakers’ Oral Proficiency

NARCIS (Netherlands)

Lahmann, Cornelia; Steinkrauss, Rasmus; Schmid, Monika

2016-01-01

There remains considerable disagreement about which factors drive second language (L2) ultimate attainment. Age of onset (AO) appears to be a robust factor, lending support to theories of maturational constraints on L2 acquisition. The present study is an investigation of factors that influence

12-lipoxygenase regulates hippocampal long-term potentiation by modulating L-type Ca2+ channels

Science.gov (United States)

DeCostanzo, Anthony J.; Voloshyna, Iryna; Rosen, Zev B.; Feinmark, Steven J.; Siegelbaum, Steven A.

2010-01-01

Although long-term potentiation (LTP) has been intensely studied, there is disagreement as to which molecules mediate and modulate LTP. This is partly due to the presence of mechanistically distinct forms of LTP that are induced by different patterns of stimulation and that depend on distinct Ca2+ sources. Here we report a novel role for the arachidonic acid-metabolizing enzyme 12-lipoxygenase (12-LO) in LTP at CA3-CA1 hippocampal synapses that is dependent on the pattern of tetanic stimulation. We find that 12-LO activity is required for the induction of LTP in response to a theta-burst stimulation (TBS) protocol, which depends on Ca2+ influx through both NMDA receptors and L-type voltage-gated Ca2+ channels. In contrast, LTP induced by 100 Hz tetanic stimulation, which requires Ca2+ influx through NMDA receptors but not L-type channels, does not require 12-LO. We find that 12-LO regulates LTP by enhancing postsynaptic somatodendritic Ca2+ influx through L-type channels during theta burst stimulation, an action exerted via 12(S)-HPETE, a downstream metabolite of 12-LO. These results help define the role of a long-disputed signaling enzyme in LTP. PMID:20130191

Long-term outcome of neuroparacoccidioidomycosis treatment

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Fabio Francesconi

2011-02-01

Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

PRE-EXERCISE ARGININE SUPPLEMENTATION INCREASES TIME TO EXHAUSTION IN ELITE MALE WRESTLERS

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H.U. Yavuz

2014-08-01

Full Text Available Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg-1 body weight or placebo was given to the subjects after 12 hours fasting (during the night for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg-1 · min-1, placebo 52.07±5.21 mL · kg-1 · min-1 or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s compared to placebo (1313±90.8 s (p<0.05. These results suggest that L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects.

Long term hypolipidaemic and anti-atherogenic effects of Carica ...

African Journals Online (AJOL)

This study was designed to assess the long term (24 weeks) effects of daily oral administration of C. papaya aqueous leaf extract (at 200 mg/kg body weight) on the serum lipid profile and other atherogenic indices of normal rabbits. Total cholesterol, total triglycerides, LDL-cholesterol, HDL-cholesterol, atherogenic and ...

Recurrent somatic embryogenesis in long-term cultures of Gentiana lutea L. as a source for synthetic seed production for medium-term preservation

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Holobiuc Irina

2012-01-01

Full Text Available Our aim was to establish an efficient and reproducible system for producing synthetic seeds from recurrent somatic embryogenesis in long-term cultures of Gentiana lutea L. This species is a vulnerable medicinal plant, protected both at the national and international levels, and is included in different Red Lists and Books. In vitro culture, as an alternative to classical methods of preservation, allows for the cyclic multiplication of plant material and short-, medium- and long-term preservation of tissue collections. Biotechnological approaches allow for maintenance of the plant material in a confined space and protection against biotic and abiotic factors. Somatic embryogenesis (SE is the most efficient way to regenerate plants, ensuring material for preservation and fundamental research. In our experiment, recurrent somatic embryogenesis was developed in long-term cultures in the presence of sugar alcohols (mannitol, sorbitol and in the absence of growth factors. This process proceeded at a high rate, with adventive somatic embryos being generated in a continuous process, followed by maturation, germination and development into plants. To follow the somatic embryogenesis process, histological samples were made. We used these embryogenic cultures for synthetic seed production and medium-term conservation. The viability of somatic embryos after moderate osmotic stress treatment was tested using TTC. Our methodology relied on the induction of somatic embryogenesis in the presence of auxins in the first cycle of in vitro cultures, long-term high embryogenic culture maintenance in the presence of sugar alcohols and synthetic seed production.

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.

Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine.

OpenAIRE

Galea, E; Regunathan, S; Eliopoulos, V; Feinstein, D L; Reis, D J

1996-01-01

Agmatine, decarboxylated arginine, is a metabolic product of mammalian cells. Considering the close structural similarity between L-arginine and agmatine, we investigated the interaction of agmatine and nitric oxide synthases (NOSs), which use L-arginine to generate nitric oxide (NO) and citrulline. Brain, macrophages and endothelial cells were respectively used as sources for NOS isoforms I, II and III. Enzyme activity was measured by the production of nitrites or L-citrulline. Agmatine was ...

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

Oral supplementations with L-glutamine or L-alanyl-L-glutamine do not change metabolic alterations induced by long-term high-fat diet in the B6.129F2/J mouse model of insulin resistance.

Science.gov (United States)

Bock, Patricia Martins; Krause, Mauricio; Schroeder, Helena Trevisan; Hahn, Gabriela Fernandes; Takahashi, Hilton Kenji; Schöler, Cinthia Maria; Nicoletti, Graziella; Neto, Luiz Domingos Zavarize; Rodrigues, Maria Inês Lavina; Bruxel, Maciel Alencar; Homem de Bittencourt, Paulo Ivo

2016-01-01

In this work, we aimed to investigate the effects of long-term supplementations with L-glutamine or L-alanyl-L-glutamine in the high-fat diet (HFD)-fed B6.129SF2/J mouse model over insulin sensitivity response and signaling, oxidative stress markers, metabolism and HSP70 expression. Mice were fed in a standard low-fat diet (STA) or a HFD for 20 weeks. In the 21th week, mice from the HFD group were allocated in five groups and supplemented for additional 8 weeks with different amino acids: HFD control group (HFD-Con), HFD + dipeptide L-alanyl-L-glutamine group (HFD-Dip), HFD + L-alanine group (HFD-Ala), HFD + L-glutamine group (HFD-Gln), or the HFD + L-alanine + L-glutamine (in their free forms) group (HFD-Ala + Gln). HFD induced higher body weight, fat pad, fasted glucose, and total cholesterol in comparison with STA group. Amino acid supplementations did not induce any modifications in these parameters. Although insulin tolerance tests indicated insulin resistance in all HFD groups, amino acid supplementations did not improve insulin sensitivity in the present model. There were also no significant differences in the immunocontents of insulin receptor, Akt, and Toll-like receptor-4. Notably, total 70 kDa heat shock protein (HSP72 + HSP73) contents in the liver was markedly increased in HFD-Con group as compared to STA group, which might suggest that insulin resistance is only in the beginning. Apparently, B6.129SF2/J mice are more resistant to the harmful effects of HFD through a mechanism that may include gut adaptation, reducing the absorption of nutrients, including amino acids, which may explain the lack of improvements in our intervention.

Assessment of long-term leaching from waste incineration air-pollution-control residues

DEFF Research Database (Denmark)

Astrup, Thomas; Mosbæk, Hans; Christensen, Thomas Højlund

2006-01-01

Assessment of long-term leaching from MSWI air-pollution-control (APC) residues is discussed with respect to use in environmental impact assessment, such as life-cycle assessment (LCA). A method was proposed for estimating leaching as a function of the liquid-to-solid (L/S) ratio in a long......-term perspective (L/S 5000l/kg). Data for changes in residue pH as a function of L/S was used in combination with pH dependent leaching data to predict leachate concentrations of Al, Ca, Cd, Ba, Mg, Ni, Pb, S, Pb, V and Zn as a function of L/S. Mass balance calculations were used to determine the element fractions...... leached with respect to L/S. The estimated long-term leaching from a semi-dry residue and a fly ash was compared with short-term leaching determined by batch tests at L/S 10l/kg, both carbonated and non-carbonated versions of the residues were investigated. Generally, very high L/S ratios above 2000l...

Self-assembled nanoparticles based on amphiphilic chitosan derivative and arginine for oral curcumin delivery

Directory of Open Access Journals (Sweden)

Raja MA

2016-09-01

Full Text Available Mazhar Ali Raja, Shah Zeenat, Muhammad Arif, Chenguang Liu College of Marine Life Science, Ocean University of China, Qingdao, Shandong, People’s Republic of China Abstract: Curcumin (Cur is a striking anticancer agent, but its low aqueous solubility, poor absorption, hasty metabolism, and elimination limit its oral bioavailability and consequently hinder its development as a drug. To redress these limitations, amphiphilic chitosan (CS conjugate with improved mucoadhesion and solubility over a wider pH range was developed by modification with hydrophobic acrylonitrile (AN and hydrophilic arginine (Arg; the synthesized conjugate (AN–CS–Arg, which was well characterized by Fourier transform infrared and 1H nuclear magnetic resonance spectroscopy. Results of critical aggregation concentration revealed that the AN–CS–Arg conjugate had low critical aggregation concentration and was prone to form self-assembled nanoparticles (NPs in aqueous medium. Cur-encapsulated AN–CS–Arg NPs (AN–CS–Arg/Cur NPs were developed by a simple sonication method and characterized for the physicochemical parameters such as zeta potential, particle size, and drug encapsulation. The results showed that zeta potential of the prepared NPs was 40.1±2.81 mV and the average size was ~218 nm. A considerable improvement in the aqueous solubility of Cur was observed after encapsulation into AN–CS–Arg/Cur NPs. With the increase in Cur concentration, loading efficiency increased but encapsulation efficiency decreased. The in vitro release profile exhibited sustained release pattern from the AN–CS–Arg/Cur NPs in typical biological buffers. The ex vivo mucoadhesion study revealed that AN–CS–Arg/Cur NPs had greater mucoadhesion than the control CS NPs. Compared with free Cur solution, AN–CS–Arg/Cur NPs showed stronger dose-dependent cytotoxicity against HT-29 cells. In addition, it was observed that cell uptake of AN–CS–Arg/Cur NPs was much higher

Beneficial Effects of Long-Term Administration of an Oral Formulation of Angiotensin-(1–7 in Infarcted Rats

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Fúlvia D. Marques

2012-01-01

Full Text Available In this study was evaluated the chronic cardiac effects of a formulation developed by including angiotensin(Ang-(1–7 in hydroxypropyl β-cyclodextrin (HPβCD, in infarcted rats. Myocardial infarction (MI was induced by left coronary artery occlusion. HPβCD/Ang-(1–7 was administered for 60 days (76 μg/Kg/once a day/gavage starting immediately before infarction. Echocardiography was utilized to evaluate usual cardiac parameters, and radial strain method was used to analyze the velocity and displacement of myocardial fibers at initial time and 15, 30, and 50 days after surgery. Real-time PCR was utilized to evaluate the fibrotic signaling involved in the remodeling process. Once-a-day oral HPβCD/Ang-(1–7 administration improved the cardiac function and reduced the deleterious effects induced by MI on TGF-β and collagen type I expression, as well as on the velocity and displacement of myocardial fibers. These findings confirm cardioprotective effects of Ang-(1–7 and indicate HPβCD/Ang-(1–7 as a feasible formulation for long-term oral administration of this heptapeptide.

Arginine Adjunctive Therapy in Active Tuberculosis

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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.

Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

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Ascher-Svanum H

2014-06-01

Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

Effect of short- and long-term feeding of L-carnitine and its congeners on the production of eicosanoids from rat peritoneal leukocytes

NARCIS (Netherlands)

Garrelds, I.M.; Elliott, G.R.; Zijlstra, F.; Bonta, I.

1994-01-01

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number

Oral features and computerized rehabilitation of a young patient with CHARGE syndrome using minimally invasive long-term interim CAD-CAM restorations.

Science.gov (United States)

Liebermann, Anja; Rafael, Caroline Freitas; Edelhoff, Daniel; Ramberger, Marc; Schweiger, Josef; Maziero Volpato, Claudia Angela; Saeidi Pour, Reza

2017-04-01

Patients with CHARGE syndrome (where CHARGE stands for coloboma of the iris or retina, heart defects or cardiac malformations, atresia/stenosis of the choanae, retardation of growth and development, genital anomalies, and ear abnormalities) present several orofacial anomalies. Their treatment depends on the specific type of manifestation. To perform the complex oral rehabilitation and achieve a conservative, esthetic, and functional exploration of the definitive treatment goal, computer-aided design and computer-aided manufacturing (CAD-CAM) polymers can be used as long-term interim restorations. This article reports the treatment of a young patient with CHARGE syndrome combined with oral alterations. CAD-CAM polymers offer an intermediate treatment with satisfying esthetics and function at low biological cost until bone growth is completed. This period facilitates additional planning for the definitive restoration. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Development and cytotoxicity of Schiff base derivative as a fluorescence probe for the detection of L-Arginine

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Shang, Xuefang; Li, Jie; Guo, Kerong; Ti, Tongyu; Wang, Tianyun; Zhang, Jinlian

2017-04-01

Inspired from biological counter parts, chemical modification of Schiff base derivatives with function groups may provide a highly efficient method to detect amino acids. Therefore, a fluorescent probe involving Schiff base and hydroxyl group has been designed and prepared, which showed high response and specificity for Arginine (Arg) among normal eighteen standard kinds of amino acids (Alanine, Valine, Leucine, Isoleucine, Methionine, Asparticacid, Glutamicacid, Arginine, Glycine, Serine, Threonine, Asparagine, Phenylalanine, Histidine, Tryptophan, Proline, Lysine, Glutamine, Tyrosine and Cysteine). Furthermore, theoretical investigation further illustrated the possible binding mode in the host-guest interaction and the roles of molecular frontier orbitals in molecular interplay. In addition, the synthesized fluorescent probe exhibited high binding ability for Arg and low cytotoxicity to MCF-7 cells over a concentration range of 0-200 μg mL-1 which can be also used as a biosensor for the Arg detection in vivo.

Long-term safety and efficacy of a novel once-weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52-week open-label, phase 3 study.

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Inagaki, Nobuya; Sano, Hiroki; Seki, Yoshifumi; Kuroda, Shingo; Kaku, Kohei

2016-09-01

Trelagliptin is a novel once-weekly oral dipeptidyl peptidase-4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long-term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus. This was a phase 3, multicenter, open-label study to evaluate long-term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end-points were the safety variables, and the secondary end-points were glycosylated hemoglobin and fasting plasma glucose. A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α-glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α-glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was -0.74 to -0.25% for each therapy. Once-weekly oral trelagliptin provides well-tolerated long-term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Are oral emergency contraceptives a safe and effective form of long-term birth control?

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Kraus, Connie; Hooper-Lane, Christopher

2017-10-01

Yes, but not as effective as some other methods. Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%; menstrual irregularity is the most common adverse effect (strength of recommendation [SOR]: B, Cochrane review of lower-quality trials). In women younger than 35 years who have sexual intercourse 6 or fewer times per month, correct and consistent use of pericoital levonorgestrel 1.5 mg results in an annual pregnancy rate of 11% (SOR: B, one large prospective, open-label trial). Pericoital contraception is less effective than long-acting reversible contraceptives (annual pregnancy rates of 0.05%-0.8%) or perfect use of combined oral contraceptives (0.3% annual pregnancy rate), but similar to, or better than, typical use of combined oral contraception (9%) and condoms (18%).

Case Reports Showing a Long-Term Effect of Subanesthetic Ketamine Infusion in Reducing L-DOPA-Induced Dyskinesias

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Scott J. Sherman

2016-02-01

Full Text Available Ketamine is an FDA-approved drug with a known safety profile. Low-dose subanesthetic intravenous ketamine infusion treatment has led to long-term reduction of treatment-resistant depression and of chronic pain states. We report on low-dose subanesthetic intravenous ketamine infusion treatment in Parkinson's disease (PD patients by 5 case studies and show a long-lasting therapeutic benefit to reduce L-DOPA-induced dyskinesia (LID, improve on time, and reduce depression. Based on the literature we hypothesize that low-dose ketamine may act as a ‘chemical deep brain stimulation', by desynchronizing hypersynchronous oscillatory brain activity, including in the basal ganglia and the motor cortex. The presented PD case reports indicate tolerability, safety and long-term beneficial effects of low-dose ketamine infusion that should be further investigated in a properly controlled prospective clinical trial for treatment of LID, as well as the prevalent nonmotor features pain and depression in PD patients.

Indian women of childbearing age do not metabolically conserve arginine as do American and Jamaican women.

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Kao, Christina C; Hsu, Jean W; Dwarkanath, Pratibha; Karnes, Jeffrey M; Baker, Tameka M; Bohren, Kurt M; Badaloo, Asha; Thame, Minerva M; Kurpad, Anura V; Jahoor, Farook

2015-05-01

In a previous study in pregnant American women, we reported that arginine flux and nitric oxide synthesis increased in trimester 2. More recently, we reported that Indian women do not increase arginine flux during pregnancy as their American or Jamaican counterparts do. The purpose of this study was to determine whether Indian women of childbearing age are producing less arginine and/or catabolizing more arginine and therefore have less available for anabolic pathways than do Jamaican and American women. Thirty healthy women aged 28.3 ± 0.8 y from the United States, India, and Jamaica (n = 10/group) were given 6 h primed, constant intravenous infusions of guanidino-¹⁵N₂-arginine, 5,5-²H₂-citrulline, ¹⁵N₂-ornithine, and ring-²H₅-phenylalanine, in addition to primed, oral doses of U-¹³C₆-arginine in both the fasting and postprandial states. An oral dose of deuterium oxide was also given to determine fat-free mass (FFM). Compared with American women, Indian and Jamaican women had greater ornithine fluxes (μmol · kg fat FFM⁻¹ · h⁻¹) in the fasting and postprandial states (27.3 ± 2.5 vs. 39.6 ± 3.7 and 37.2 ± 2.0, respectively, P = 0.01), indicating greater arginine catabolism. However, Jamaican women had a higher endogenous arginine flux than did Indian and American women in the fasting (66.1 ± 3.1 vs. 54.2 ± 3.1 and 56.1 ± 2.1, respectively, P = 0.01) and postprandial (53.8 ± 2.2 vs. 43.7 ± 4.9 and 42.8 ± 3.1, respectively, P = 0.06) states. As a consequence, Indian women had lower arginine bioavailability (μmol · kg FFM⁻¹ · h⁻¹) in the fasting state (42.0 ± 2.6) than did American (49.9 ± 1.3, P = 0.045) and Jamaican (55.5 ± 3.5, P = 0.004) women, as well as in the postprandial state (40.7 ± 3.5 vs. 51.8 ± 1.2 and 57.5 ± 3.2, respectively, P = 0.001). Compared with American and Jamaican women, Indian women of childbearing age have a decreased arginine supply because of increased arginine catabolism without an

Independent inactivation of arginine decarboxylase genes by nonsense and missense mutations led to pseudogene formation in Chlamydia trachomatis serovar L2 and D strains

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Graham David E

2009-07-01

Full Text Available Abstract Background Chlamydia have reduced genomes that reflect their obligately parasitic lifestyle. Despite their different tissue tropisms, chlamydial strains share a large number of common genes and have few recognized pseudogenes, indicating genomic stability. All of the Chlamydiaceae have homologs of the aaxABC gene cluster that encodes a functional arginine:agmatine exchange system in Chlamydia (Chlamydophilapneumoniae. However, Chlamydia trachomatis serovar L2 strains have a nonsense mutation in their aaxB genes, and C. trachomatis serovar A and B strains have frameshift mutations in their aaxC homologs, suggesting that relaxed selection may have enabled the evolution of aax pseudogenes. Biochemical experiments were performed to determine whether the aaxABC genes from C. trachomatis strains were transcribed, and mutagenesis was used to identify nucleotide substitutions that prevent protein maturation and activity. Molecular evolution techniques were applied to determine the relaxation of selection and the scope of aax gene inactivation in the Chlamydiales. Results The aaxABC genes were co-transcribed in C. trachomatis L2/434, during the mid-late stage of cellular infection. However, a stop codon in the aaxB gene from this strain prevented the heterologous production of an active pyruvoyl-dependent arginine decarboxylase. Replacing that ochre codon with its ancestral tryptophan codon rescued the activity of this self-cleaving enzyme. The aaxB gene from C. trachomatis D/UW-3 was heterologously expressed as a proenzyme that failed to cleave and form the catalytic pyruvoyl cofactor. This inactive protein could be rescued by replacing the arginine-115 codon with an ancestral glycine codon. The aaxC gene from the D/UW-3 strain encoded an active arginine:agmatine antiporter protein, while the L2/434 homolog was unexpectedly inactive. Yet the frequencies of nonsynonymous versus synonymous nucleotide substitutions show no signs of relaxed

Pituitary diseases : long-term psychological consequences

NARCIS (Netherlands)

Tiemensma, Jitske

2012-01-01

Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

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

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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

Relationship of a turbidity of an oral rinse with oral health and malodor in Vietnamese patients.

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Pham, Thuy A V

2014-05-01

In the present study, the relationship between the turbidity of mouth-rinse water and oral health conditions, including oral malodor, in patients with (n = 148) and without (n = 231) periodontitis was examined. The turbidity of 20 mL distilled water that the patients rinsed in their mouths 10 times was measured using a turbidimeter. Oral malodor was evaluated using an organoleptic test and Oral Chroma. Oral health conditions, including decayed teeth, periodontal status, oral hygiene status, proteolytic activity of the N-benzoyl-dl-arginine-2-napthilamide (BANA) test on the tongue coating, and salivary flow rate, were assessed. Turbidity showed significant correlations with oral malodor and all oral health parameters in the periodontitis group. In the non-periodontitis group, turbidity showed significant correlations with oral malodor and oral health parameters, including dental plaque, tongue coating, BANA test, and salivary flow rate. The regression analysis indicated that turbidity was significantly associated with methyl mercaptan and the BANA test in the periodontitis group, and with hydrogen sulfide, dental plaque, tongue coating, and salivary flow rate in the non-periodontitis group. The findings of the present study indicate that the turbidity of mouth-rinse water could be used as an indicator of oral health conditions, including oral malodor. © 2013 Wiley Publishing Asia Pty Ltd.

Dental implant status of patients receiving long-term nursing care in Japan.

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Kimura, Toru; Wada, Masahiro; Suganami, Toru; Miwa, Shunta; Hagiwara, Yoshiyuki; Maeda, Yoshiobu

2015-01-01

The increase in implant patients is expected to give rise to a new problem: the changing general health status of those who have had implants placed. The aim of this present study was to find out the needs of and proper measures for elderly implant patients in long-term care facilities. A questionnaire was sent by mail to 1,591 long-term care health facilities, daycare services for people with dementia, and private nursing homes for the elderly in the Osaka area, which is in the middle area of Japan, in order to extract patients with cerebrovascular disease or dementia who were possibly at risk of inadequate oral self-care, as well as patients with implants. Approximately half of all facilities responded that they cannot recognize implants, and many facilities did not know anything about oral care for implant patients. Residents with implants were reported at 19% of all facilities. Also, the facilities pointed out problems with implants relating to the difference in oral care between implants and natural teeth. There are people with implants in some 20% of caregiving facilities, and there is a low level of understanding regarding implants and their care among nurses and care providers who are providing daily oral care. © 2013 Wiley Periodicals, Inc.

Effect of Long-Term Consumption of Lactobacillus paracasei SD1 on Reducing Mutans streptococci and Caries Risk: A Randomized Placebo-Controlled Trial

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Rawee Teanpaisan

2015-04-01

Full Text Available Background: A previous study revealed Lactobacillus paracasei SD1, a probiotic strain, could reduce mutans streptococci (MS. The aim of this study was to evaluate the long-term effects of L. paracasei SD1 on the colonization of MS, and whether caries lesions developed. Methods: After informed consent, 122 children were recruited and randomly assigned to the probiotic or control groups. The probiotic group received milk-powder containing L. paracasei SD1 and the control group received standard milk-powder once daily for six months. Salivary MS and lactobacilli were enumerated using differential culture at baseline and at three-month intervals for 12 months. The persistence of L. paracasei SD1 was investigated using AP-PCR for DNA-fingerprinting. Oral health was examined at baseline and at the end of the study according to WHO criteria. Results: The long-term consumption could prolong colonization of L. paracasei SD1. Significantly reduced MS counts and increased lactobacilli levels were found among children in the probiotic group. There were less caries lesions in the probiotic group at the end of the study. A significant reduction of the development of new caries lesions (4.5 times was observed in the high caries risk group but not in the low caries risk group. Conclusions: Results demonstrate that the long-term daily ingestion of the human-derived probiotic L. paracasei SD1 significantly reduces the number of MS and caries risk in the high caries group.

Vitamin D status among long-term survivors of testicular cancer.

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Schepisi, Giuseppe; De Padova, Silvia; Scarpi, Emanuela; Lolli, Cristian; Gurioli, Giorgia; Menna, Cecilia; Burgio, Salvatore L; Rossi, Lorena; Gallà, Valentina; Casadio, Valentina; Salvi, Samanta; Conteduca, Vincenza; De Giorgi, Ugo

2017-05-30

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

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...

Short communication: Modulation of the small intestinal microbial community composition over short-term or long-term administration with Lactobacillus plantarum ZDY2013.

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Xie, Qiong; Pan, Mingfang; Huang, Renhui; Tian, Ximei; Tao, Xueying; Shah, Nagendra P; Wei, Hua; Wan, Cuixiang

2016-09-01

The small intestinal (SI) microbiota has an essential role in the maintenance of human health. However, data about the indigenous bacteria in SI as affected by probiotics are limited. In our study, the short-term and long-term effects of a probiotic candidate, Lactobacillus plantarum ZDY2013, on the SI microbiota of C57BL/6J mice were investigated by the Illumina HiSeq (Novogene Bioinformatics Technology Co., Ltd., Tianjin, China) platform targeting the V4 region of the 16S rDNA. A total of 858,011 sequences in 15 samples were read. The α diversity analysis revealed that oral administration with L. plantarum ZDY2013 for 3 wk led to a significant increase in the richness and diversity of the SI bacterial community. Principal coordinate analysis and unweighted pair-group method with arithmetic means analysis showed a clear alteration in the SI microbiota composition after 3 wk of L. plantarum ZDY2013 treatment, although these changes were not found 6 wk after ceasing L. plantarum ZDY2013 administration. Species annotation showed that the dominant phyla in SI microbiota were Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia. Interestingly, operational taxonomic unit cluster analysis showed that administration with L. plantarum ZDY2013 for 3 wk significantly increased the abundance of Proteobacteria, but decreased that of Bacteroidetes. Linear discriminant analysis coupled with effect size identified 18 bacterial taxa (e.g., Ruminococcus spp. and Clostridium spp.) that overgrew in the SI microbiota of the mice administered with L. plantarum ZDY2013 for 3 wk, and most of them belonged to the phyla Bacteroidetes and Proteobacteria. However, only one bacterial taxon (e.g., Nocardioides spp.) was over-represented in the SI microbiota of mice 6 wk after L. plantarum ZDY2013 administration. Overall, this study shows that oral administration with probiotic results in an important but transient alteration in the microbiota of SI. Copyright © 2016 American Dairy

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice

DEFF Research Database (Denmark)

Chennupati, Ramesh; Meens, Merlijn J P M T; Marion, Vincent

2014-01-01

AIM: Argininosuccinate synthetase (ASS) is essential for recycling L-citrulline, the by-product of NO synthase (NOS), to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice. METHODS...... of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting...... responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar...

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

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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

Long-term iron deficiency: Tracing changes in the proteome of different pea (Pisum sativum L.) cultivars.

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Meisrimler, Claudia-Nicole; Wienkoop, Stefanie; Lyon, David; Geilfus, Christoph-Martin; Lüthje, Sabine

2016-05-17

Iron deficiency (-Fe) is one of the major problems in crop production. Dicots, like pea (Pisum sativum L.), are Strategy I plants, which induce a group of specific enzymes such as Fe(III)-chelate reductase (FRO), Fe responsive transporter (IRT) and H(+)-ATPase (HA) at the root plasma membrane under -Fe. Different species and cultivars have been shown to react diversely to -Fe. Furthermore, different kinds of experimental set-ups for -Fe have to be distinguished: i) short-term vs. long-term, ii) constant vs. acute alteration and iii) buffered vs. unbuffered systems. The presented work compares the effects of constant long-term -Fe in an unbuffered system on roots of four different pea cultivars in a timely manner (12, 19 and 25days). To differentiate the effects of -Fe and plant development, control plants (+Fe) were analyzed in comparison to -Fe plants. Besides physiological measurements, an integrative study was conducted using a comprehensive proteome analysis. Proteins, related to stress adaptation (e.g. HSP), reactive oxygen species related proteins and proteins of the mitochondrial electron transport were identified to be changed in their abundance. Regulations and possible functions of identified proteins are discussed. Pea (Pisum sativum L.) belongs to the legume family (Fabaceae) and is an important crop plant due to high Fe, starch and protein contents. According to FAOSTAT data (September 2015), world production of the garden pea quadrupled from 1970 to 2012. Since the initial studies by Gregor Mendel, the garden pea became the most-characterized legume and has been used in numerous investigations in plant biochemistry and physiology, but is not well represented in the "omics"-related fields. A major limitation in pea production is the Fe availability from soils. Adaption mechanisms to Fe deficiency vary between species, and even cultivars have been shown to react diversely. A label-free proteomic approach, in combination with physiological measurements

Driving ability in cancer patients receiving long-term morphine analgesia.

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Vainio, A; Ollila, J; Matikainen, E; Rosenberg, P; Kalso, E

1995-09-09

When given in single doses to healthy volunteers, opioid analgesics impair reaction time, muscle coordination, attention, and short-term memory sufficiently to affect driving and other skilled activities. Despite the increasing use of oral morphine daily, little is known about the effect of long-term opioid therapy on psychomotor performance. To examine the effects of continuous morphine medication, psychological and neurological tests originally designed for professional motor vehicle drivers were conducted in two groups of cancer patients who were similar apart from experience of pain. 24 were on continuous morphine (mean 209 mg oral morphine daily) for cancer pain; and 25 were pain-free without regular analgesics. Though the results were a little worse in the patients taking morphine, there were no significant differences between the groups in intelligence, vigilance, concentration, fluency of motor reactions, or division of attention. Of the neural function tests, reaction times (auditory, visual, associative), thermal discrimination, and body sway with eyes open were similar in the two groups; only balancing ability with closed eyes was worse in the morphine group. These results indicate that, in cancer patients receiving long-term morphine treatment with stable doses, morphine has only a slight and selective effect on functions related to driving.

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.

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.

Short- and long-term changes in sugarbeet (Beta vulgaris L. gene expression due to postharvest jasmonic acid treatment - Data

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Lucilene Silva de Oliveira

2017-04-01

Full Text Available Jasmonic acid is a natural plant hormone that induces native defense responses in plants. Sugarbeet (Beta vulgaris L. root unigenes that were differentially expressed 2 and 60 days after a postharvest jasmonic acid treatment are presented. Data include changes in unigene expression relative to water-treated controls, unigene annotations against nonredundant (Nr, Swiss-Prot, Clusters of Orthologous Groups (COG, and Kyoto Encyclopedia of Genes and Genomes (KEGG protein databases, and unigene annotations with Gene Ontology (GO terms. Putative defense unigenes are compiled and annotated against the sugarbeet genome. Differential gene expression data were generated by RNA sequencing. Interpretation of the data is available in the research article, “Jasmonic acid causes short- and long-term alterations to the transcriptome and the expression of defense genes in sugarbeet roots” (K.K. Fugate, L.S. Oliveira, J.P. Ferrareze, M.D. Bolton, E.L. Deckard, F.L. Finger, 2017 [1]. Public dissemination of this dataset will allow further analyses of the data.

Influence of halogen irradiance on short- and long-term wear resistance of resin-based composite materials.

LENUS (Irish Health Repository)

Bhamra, Gurcharn S

2009-02-01

The Oregon Health Science University (OHSU) four-chamber oral wear simulator was used to examine the impact of halogen irradiance on the short- and long-term wear behavior of four-methacrylate resin-based composites (RBCs). The hypothesis proposed was that exacerbated wear would occur following the long-term wear of RBCs irradiated under non-optimized irradiance conditions.

Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine

DEFF Research Database (Denmark)

Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev

2015-01-01

–arginine in a larger production scale. In this work, a tablet formulation was developed for a co-amorphous salt, namely spray dried indomethacin–arginine (SD IND–ARG). The effects of compaction pressure on tablet properties, physical stability and dissolution profiles under non-sink conditions were examined....... Dissolution profiles of tablets with SD IND–ARG (TAB SD IND–ARG) were compared to those of tablets containing a physical mixture of crystalline IND and ARG (TAB PM IND–ARG) and to the dissolution of pure spray dried powder. Concerning tableting, the developed formulation allowed for the preparation of tablets...... with a broad range of compaction pressures resulting in different porosities and tensile strengths. XRPD results showed that, overall, no crystallization occurred neither during tableting nor during long-term storage. Dissolution profiles of TAB SD IND–ARG showed an immediate release of IND by erosion...

[An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

Science.gov (United States)

Sakaguchi, Hideo

2014-06-01

Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33 males, 69 females, mean age: 76.9 +/- 5.7) considered to be in potential need of long-term social care and attending a long-term care prevention class in Sayama City, Saitama Prefecture, Japan. The degree of improvement in oral functions (7 items) and oral hygienic conditions (3 items) was assessed by comparing oral health before and after participation in the program. The results showed statistically significant improvements in the following oral functions: (1) lip functions (oral diadochokinesis, measured by the regularity of the repetition of the syllable "Pa"), (2) tongue functions, (3) tongue root motor skills (oral diadochokinesis, measured by the regularity of the repetition of the syllables "Ta" and "Ka"), (4) tongue extension/retraction, (5) side-to-side tongue movement functions, (6) cheek motor skills, and (7) repetitive saliva swallowing test (RSST). The following measures of oral hygiene also showed a statistically significant improvement: (1) debris on dentures or teeth, (2) coated tongue, and (3) frequency of oral cleaning. These findings demonstrated that an improvement program informed by health behavior theories is useful in improving oral functions and oral hygiene conditions.

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.

Long-term success of oral health intervention among care-dependent institutionalized seniors: Findings from a controlled clinical trial.

Science.gov (United States)

Schwindling, Franz Sebastian; Krisam, Johannes; Hassel, Alexander J; Rammelsberg, Peter; Zenthöfer, Andreas

2018-04-01

The purpose of this work was to investigate the long-term effectiveness of oral health education of caregivers in nursing homes with care-dependent and cognitively impaired residents. Fourteen nursing homes with a total of 269 residents were allocated to a control group, with continued normal care, or to an intervention group. Allocation was performed at nursing home level. In the intervention group, caregivers were given oral health education, and ultrasonic cleaning devices were provided to clean removable prostheses. Oral health was assessed at baseline and after 6 and 12 months by use of the Plaque Control Record (PCR), Gingival Bleeding Index (GBI), Community Periodontal Index of Treatment Needs (CPITN) and Denture Hygiene Index (DHI). Mixed models for repeated measures were performed for each target variable, with possible confounding factors (intervention/control group, age, sex, residence location and care-dependence). In the control group, no changes of target variables were observed between baseline and the 6- and 12-month follow-ups. After 6 and 12 months, PCR and DHI were significantly improved in the intervention group. For PCR, the intergroup difference of improvements was -14.4 (95% CI: -21.8; -6.9) after 6 months. After 12 months, the difference was -16.2 (95% CI: -27.7; -4.7). For DHI, the intergroup difference compared to baseline was -15 (95% CI: -23.6; -6.5) after 6 months and -13.3 (95% CI: -24.9; -1.8) after 12 months. There was neither a statistically significant effect on GBI nor on CPITN. Care-dependency showed a substantial trend to smaller improvements in PCR (P = .074), while an inverse effect was apparent for DHI (P < .001). Education of caregivers improves and maintains the oral health of care-dependent nursing home residents over longer periods. Use of ultrasonic devices is a promising means of improving denture hygiene among the severely care-dependent. Such interventions can be easily and cheaply implemented in routine daily care. �

Long-term opioid therapy in Denmark

DEFF Research Database (Denmark)

Birke, H; Ekholm, Ola; Sjøgren, P

2017-01-01

significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4

Directory of Open Access Journals (Sweden)

Shinji Yamada

2018-03-01

Full Text Available Programmed cell death-ligand 1 (PD-L1, which is a ligand of programmed cell death-1 (PD-1, is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1 expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb, L1Mab-4 (IgG2b, kappa, using cell-based immunization and screening (CBIS method and investigated hPD-L1 expression in oral cancers. L1Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 in flow cytometry and stained oral cancers in a membrane-staining pattern. L1Mab-4 stained 106/150 (70.7% of oral squamous cell carcinomas, indicating the very high sensitivity of L1Mab-4. These results indicate that L1Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers. Keywords: Programmed cell death-ligand 1, Monoclonal antibody, Oral cancer

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

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

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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

Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2013-12-01

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-term leaching of nutrients and contaminants from wood combustion ashes

DEFF Research Database (Denmark)

Maresca, Alberto; Hyks, J.; Astrup, Thomas Fruergaard

2018-01-01

With increasing amounts of woody biomass being combusted for energy purposes worldwide, more wood ash is being generated and needs management. As an alternative to landfilling, residues may be utilised for liming and fertilising purposes on forest soils. Comprehensive evaluations of long-term lea......With increasing amounts of woody biomass being combusted for energy purposes worldwide, more wood ash is being generated and needs management. As an alternative to landfilling, residues may be utilised for liming and fertilising purposes on forest soils. Comprehensive evaluations of long......-term leaching from these residues are needed in order to assess potential environmental impacts associated with their utilisation. Two Danish wood ash samples, one fly ash and one mixed ash (a combination of fly ash and bottom ash), were evaluated in long-term percolation column tests (up to L/S ∼2000 L....../kg), in order to quantify the release of major, minor and trace metal(loid)s. While columns of three different lengths were used, the leaching of individual elements could be described as a function of the L/S ratio – irrespective of the column length. At L/S 1000 L/kg, the cumulative releases of K, S, Na, Ca...

Investigation of the treatment results of advanced squamous cell carcinoma of the oral cavity and clinical necessity of long-term follow-up

International Nuclear Information System (INIS)

Yamakawa, Nobuhiro; Kirita, Tadaaki; Imai, Yuichiro; Yamanaka, Yasutsugu; Aoki, Kumiko

2011-01-01

It has been considered that oral cancer is cured if more than five years pass without recurrence or metastasis after the initial treatment. Treatment results are usually evaluated as a 5-year survival rate, but we sometimes find recurrence more than five years after the initial treatment. We retrospectively investigated treatment results by long-term follow-up of advanced squamous cell carcinoma of the oral cavity after radical surgery, and analyzed the relation between the period of follow-up and the time to recurrence. One hundred and sixteen patients with advanced squamous cell carcinoma of the oral cavity were enrolled between November 1994 and October 2004 in this study. Seventy-six patients were Stage III and 40 were stage IV, and the mean age of this cohort was 63.0 years. All patients received radical surgery with or without preoperative chemoradiotherapy and were followed for a minimum of 5 years. Overall actuarial survival of all patients was 77.8% at 10 years. The 10-year cumulative local and regional recurrence rates were 20.1% and 12.9%, respectively. The actuarial loco-regional recurrence rate was the highest within 2 years after initial treatment at 19.0%, and was seen in 3.4% even after 5 years. These results showed that it is necessary to follow-up patients with advanced oral cancer even beyond 5 years after the initial treatment because there was delayed loco-regional recurrence in 3.4%. (author)

Nitric-oxide supplementation for treatment of long-term complications in argininosuccinic aciduria

Science.gov (United States)

Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea cycle disorder, and leads to deficiency of both urea...

Detection of high PD-L1 expression in oral cancers by a novel monoclonal antibody L1Mab-4.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Kaneko, Mika K; Kato, Yukinari

2018-03-01

Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L 1 Mab-4 (IgG 2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers. L 1 Mab-4 reacted with oral cancer cell lines (Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4) in flow cytometry and stained oral cancers in a membrane-staining pattern. L 1 Mab-4 stained 106/150 (70.7%) of oral squamous cell carcinomas, indicating the very high sensitivity of L 1 Mab-4. These results indicate that L 1 Mab-4 could be useful for investigating the function of hPD-L1 in oral cancers.

Long-term follow-up in dogs with idiopathic eosinophilic bronchopneumopathy treated with inhaled steroid therapy.

Science.gov (United States)

Canonne, A M; Bolen, G; Peeters, D; Billen, F; Clercx, C

2016-10-01

Treatment of canine idiopathic eosinophilic bronchopneumopathy mainly consists of long-term oral corticosteroid therapy. To avoid side effects, inhaled steroid therapy has been increasingly used but long-term clinical response and potential side effects are sparsely described. Description of clinical response and side effects with long-term fluticasone in dogs with eosinophilic bronchopneumopathy. Case series of dogs with eosinophilic bronchopneumopathy and treated with fluticasone monotherapy for at least 6 months. Clinical response and side effects assessed by physical examination, standardised questionnaire and ACTH (corticotropin) stimulation test. Eight dogs were treated for between 6 months and 5 years. Cough initially improved in all dogs; two dogs remained free of clinical signs, three were well controlled, but three showed severe relapse. Pituitary-adrenal axis inhibition occurred in two dogs treated with fluticasone monotherapy for more than 2 years; only one dog had clinical signs of iatrogenic hyperadrenocorticism. Fluticasone monotherapy allows initial improvement or remission in the majority of dogs but long-term treatment fails to resolve the cough in some individuals. In addition, such therapy may induce pituitary-adrenal axis inhibition. Prospective larger and randomised studies including both fluticasone and orally-treated dogs are needed to define the optimal treatment. © 2016 British Small Animal Veterinary Association.

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

Directory of Open Access Journals (Sweden)

Wax Benjamin

2012-04-01

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

Synthesis, characterization and behaviour of trans-bis (argininate) copper (II) to gamma radiation

International Nuclear Information System (INIS)

Pereira, A.B.

1984-01-01

The synthesis, the characterization and the behaviour to gamma radiation of trans-bis (argininate) copper (II) are presented. The synthesis is made from copper sulfate, sodium hydroxide and hydrochloride of L (+) arginine, in aqueous medium, and the characterization by infrared spectroscopy, visible and ultraviolet spectroscopy and elementary analysis. (C.G.C.)

Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

Directory of Open Access Journals (Sweden)

Ciudad A

2013-11-01

Full Text Available Antonio Ciudad,1 Ernie Anand,2 Lovisa Berggren,3 Marta Casillas,4 Alexander Schacht,3 Elena Perrin5 1Department of Clinical Research and Development, Eli Lilly & Co, Madrid, Spain; 2Neuroscience Medical Affairs – EU, Lilly Research Centre, Windlesham, Surrey, UK; 3Global Statistical Sciences, Eli Lilly & Co, Bad Homburg, Germany; 4European Scientific Communications, Eli Lilly & Co, Madrid, Spain; 5Medical Department, Eli Lilly & Co, Suresnes, Paris, France Background: A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI from either oral olanzapine (OLZ or other antipsychotics (non-OLZ. Methods: Post hoc analyses were done based on two randomized studies (one short-term, one long-term conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results: These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209 or long-term study (P=0.448. Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198 or long-term (57.1% versus 47.8% respectively; P=0.238 studies. In the short-term study, no

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)

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.

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

Directory of Open Access Journals (Sweden)

Lori A Coburn

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

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.

Long standing intra oral acid burn

NARCIS (Netherlands)

Kumar, V.V.; Ebenezer, S.; Lobbezoo, F.

2015-01-01

Oral burn due to ingestion of corrosive substances can bring about debilitating consequences. It often brings mortality, and the survivors can have severe impairment of functions, especially in relation to the stomatognathic and gastrointestinal systems. This article presents a long-standing case

Children?s oral health-related quality of life and associated factors: Mid-term changes after dental treatment under general anesthesia

OpenAIRE

Baghdadi, Ziad D.

2015-01-01

Objectives: This study aimed to document the mid-term effects of comprehensive dental treatment under general anesthesia (DTGA) on parent-assessed children?s oral health-related quality of life (COHRQoL). A second aim was to examine some epidemiological factors associated with COHRQoL and treatment outcome. Study Design: A pretest-posttest design was followed in which parents were surveyed using the Child Oral Health Quality of Life Questionnaire before and 6-9 months after their children (ag...

Decayed, missing and filled teeth index and dental anomalies in long-term survivors leukaemic children: a prospective controlled study.

Science.gov (United States)

Lauritano, Dorina; Petruzzi, Massimo

2012-11-01

The aim of this prospective controlled study is the comparison between long-term children survived leukaemia and a control group in terms of the decayed, missing or filled permanent teeth (DMFT) and dental anomalies. Fifty-two long term children survived leukaemia, aged from 8 to 15 years (27 females, 25 males; mean age 11.5 years) were evaluated for the possible effects of the anti-leukaemic therapy on dental development and compared to a control group of 52 healthy children (27 females, 25 males, mean age 11 years). All long-term children who survived were at least 24 months in continuous complete remission. The study of the dental status with a routine oral examination and panoramic radiographs was performed. The DMFT (recorded according to the WHO criteria) and dental anomalies were registered and evaluated. The results of this study evidence that long-term children survived leukaemia, in comparison with the control group, have an higher risk to develop dental caries and show a greater severity of dental anomalies including V-shaped roots, dental agenesis, microdontia, enamel dysplasias. Paediatric patients with haemathological diseases require a special attentions in dental care in addition to the antineoplastic treatment. Therefore, oral hygiene and oral health can be maintained thanks to a close cooperation between the paediatric oncohaematologists, pediatrics dental surgeons and dental hygienists.

Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency

Directory of Open Access Journals (Sweden)

Brissette Suzanne

2011-07-01

Full Text Available Abstract Background Substitution with opioid-agonists (e.g., methadone has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST. In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes. Methods Data from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI, conducted in Vancouver and Montreal (Canada between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8 was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group. Results A total of 232 (92% and 237 (94% participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by

Long-term psychosocial consequences of surgical congenital malformations.

Science.gov (United States)

Diseth, Trond H; Emblem, Ragnhild

2017-10-01

Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes

Science.gov (United States)

Fraser, David A.; Diep, Lien M.; Hovden, Inger Anette; Nilsen, Kristian B.; Sveen, Kari Anne; Seljeflot, Ingebjørg; Hanssen, Kristian F.

2012-01-01

OBJECTIVE To study the effects of long-term oral benfotiamine supplementation on peripheral nerve function and soluble inflammatory markers in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS The study randomly assigned 67 patients with type 1 diabetes to receive 24-month benfotiamine (300 mg/day) or placebo supplementation. Peripheral nerve function and levels of soluble inflammatory variables were assessed at baseline and at 24 months. RESULTS Fifty-nine patients completed the study. Marked increases in whole-blood concentrations of thiamine and thiamine diphosphate were found in the benfotiamine group (both P benfotiamine (300 mg/day) supplementation over 24 months has no significant effects upon peripheral nerve function or soluble markers of inflammation in patients with type 1 diabetes. PMID:22446172

Audit of long-term and short-term liabilities

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Korinko M.D.

2017-03-01

Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

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Takashi Kondoh

2010-06-01

Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

The Ergogenic Potential of Arginine

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La Bounty Paul M

2004-12-01

Full Text Available Abstract Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1 its role in the secretion of endogenous growth hormone; 2 its involvement in the synthesis of creatine; 3 its role in augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a review of clinical investigations involving exercise performance and arginine ingestion.

Evaluation of a dentifrice containing 8% arginine, calcium carbonate, and sodium monofluorophosphate to repair acid-softened enamel using an intra-oral remineralization model.

Science.gov (United States)

Sullivan, R; Rege, A; Corby, P; Klaczany, G; Allen, K; Hershkowitz, D; Goldder, B; Wolff, M

2014-01-01

An intra-oral remineralization study was conducted to compare the ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to remineralize acid-softened bovine enamel specimens compared to a silica-based dentifrice with 1450 ppm fluoride as MFP. The intra-oral clinical study employed a double blind, two-treatment, crossover design, and used an upper palatal retainer to expose the enamel specimens to the oral environment during product use and periods of remineralization. The retainer was designed to house three partially demineralized bovine enamel samples. The study population was comprised of 30 adults, ages 18 to 70 years. The study consisted of two treatment phases with a washout period lasting seven (+/- three) days preceding each treatment phase. A silica-based dentifrice without fluoride was used during the washout period. The Test Dentifrice used in this study contained 8% arginine, calcium carbonate, and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The treatment period consisted of a three-day lead-in period with the assigned product. The panelists brushed two times per day during the three-day lead-in period with the assigned product. On the fourth day, the panelists began brushing with the assigned product with the retainer in their mouth. The panelists brushed for one minute, followed by a one-minute swish with the slurry and a rinse with 15 ml of water in the morning, in the afternoon, and night with the retainer in the mouth. The panelists brushed only their teeth and not the specimens directly. Changes in mineral content before and after treatment were measured using a Knoop microhardness tester. The results of the study showed that percent remineralization values for the Test Dentifrice and Control Dentifrice were 14.99% and 8.66%, respectively. A statistical analysis

Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

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Magdalena M Przybycien-Szymanska

2011-04-01

Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

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.

Long-term effect of 90Y pituitary implantation in acromegaly

International Nuclear Information System (INIS)

Jadresic, A.; Jimenez, L.E.; Joplin, G.F.

1987-01-01

This report examines the long-term trends in GH levels and pituitary function in a group of 38 acromegalic patients who were selected insofar as we were able to follow them up for more than 10 years after a single dose 90 Y interstitial pituitary irradiation as the sole treatment. Mean serum GH had fallen from 106 to 24 mIU/l within 3-6 months and then slowly declined to 4 mIU/l after 10 years. GH levels of ≤5 mIU/l during a 50 g oral glucose tolerance test were obtained in 8% of patients at 3-6 months and in 18% at 1 year, the cumulative percentage increasing to 53% at 10, and 76% at 14 years. The percentage of patients requiring hormone replacement therapy rose from nil pre-implant to 16% by 3-6 months, and then slowly increased to 39% by 14 years. Serial coned radiographs of the pituitary fossa were available for 32 patients. By 10 years, 16 showed thickening of the dorsum sellae and/or reduction of at least one diameter by 3 mm. Concerning symptoms, all 29 patients whose GH level fell to ≤5 mIU/l showed improvements, 22 becoming asymptomatic. Seven patients with lesser falls in GH levels (from a mean of 193 to a mean of 15 mIU/l) all improved, one becoming asymptomatic. Two showed no variation. These results show that 90 Y pituitary implants have a cumulative effect over the years in inducting remission and hypopituitarism in acromegalic patients, the early decline in GH levels being swifter than from other forms of irradiation. (author)

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.

Long-Term Intermittent Exposure to High Altitude Elevates Asymmetric Dimethylarginine in First Exposed Young Adults.

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Lüneburg, Nicole; Siques, Patricia; Brito, Julio; De La Cruz, Juan José; León-Velarde, Fabiola; Hannemann, Juliane; Ibanez, Cristian; Böger, Rainer H

2017-09-01

Lüneburg, Nicole, Patricia Siques, Julio Brito, Juan José De La Cruz, Fabiola León-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Böger. Long-term intermittent exposure to high altitude elevates asymmetric dimethylarginine in first exposed young adults. High Alt Med Biol. 18:226-233, 2017.-Hypoxia-induced dysregulation of pulmonary and cerebral circulation may be related to an impaired nitric oxide (NO) pathway. We investigated the effect of chronic intermittent hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA) and assessed their associations with acclimatization in male draftees (n = 72) undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased from 1.14 ± 0.04 to 1.95 ± 0.09 μmol/L (mean ± SE) and from 0.22 ± 0.07 to 0.39 ± 0.03 μmol/L, respectively, (p < 0.001 for both) after 3 months, whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in CH (3.48 ± 0.07, 0.53 ± 0.08 μmol/L; p < 0.001) as compared with CIH. In both CIH and CH, ADMA correlated with hematocrit (r 2  = 0.07, p < 0.05; r 2  = 0.26; p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L-NMMA, are elevated in hypoxia. This may contribute to impaired NO production at altitude and may also be predictive of altitude-associated health impairment.

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.

Clinical Outcome And Arginine Serum of Acute Ischemic Stroke Patients Supplemented by Snakehead Fish Extract

Science.gov (United States)

Pudjonarko, Dwi; Retnaningsih; Abidin, Zainal

2018-02-01

Background: Levels of arginine associated with clinical outcome in acute ischemic stroke (AIS). Arginine is a protein needed to synthesis nitric oxide (NO), a potential vasodilator and antioxidant. Snakehead fish is a source of protein which has antioxidant activity. Snakehead fish contains mineral, vitamin, and amino acids. One of the amino acids that were found quite high in snakehead fish extract is arginine. The aim of this study was done to determine the effect of snakehead fish extracts (SFE) on serum arginin levels and clinical outcome of AIS patients. Methods: It was double-blind randomized pretest-posttest control group design, with. AIS patients were divided into two groups i.e. snakehead fish extracts (SFE) and control. SFE group were administered 15 grams SFE for 7 days . Arginine serum levels and clinical outcome (measured by National Institute of Health Stroke Scale = NIHSS) were measured before and after treatment, other related factors were also analyzed in Logistic regression. Results: A total of 42 subjects who were performed random allocation as SFE or control group. There was no differences in subject characteristics between the two groups. There was a differences Δ arginine serum levels between SFE and control (33.6±19.95 μmol/L 0.3±2.51 μmol/L pgender factor that affected on improvement of NIHSS (OR=7; p=0,01). Conclusion: There is Clinical outcome improvement and enhancement of arginine serum levels in AIS patient with snakehead fish extract supplementation.

The potential benefits of a new poliovirus vaccine for long-term poliovirus risk management.

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Duintjer Tebbens, Radboud J; Thompson, Kimberly M

2016-12-01

To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

Long-term follow-up study and long-term care of childhood cancer survivors

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Hyeon Jin Park

2010-04-01

Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories.

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Hardt, Oliver; Nader, Karim; Wang, Yu-Tian

2014-01-05

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

Dynamique long-terme de l'érosion en contexte cratonique : l'Afrique de l'Ouest depuis l'Eocène

OpenAIRE

Grimaud , Jean-Louis

2014-01-01

The long-term (107 yr) erosion dynamics of cratonic domains is studied in the present thesis based on the spatial analysis of paleolandsurfaces preserved at the scale of West Africa (~ 4 x 106 km2) since Eocene times. One shows that the West African drainage (i.e. Niger and Volta) was established 24 my ago. Since then, river long profiles have slightly evolved while the position of major knickzones was stabilized on lithological contrasts. The deformation of these profiles was used for gaugin...

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

Science.gov (United States)

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease

Further studies of the effects of aging on arginine metabolites in the rat vestibular nucleus and cerebellum.

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Liu, P; Gupta, N; Jing, Y; Collie, N D; Zhang, H; Smith, P F

2017-04-21

Some studies have demonstrated that aging is associated with impaired vestibular reflexes, especially otolithic reflexes, resulting in postural instability. However, the neurochemical basis of these age-related changes is still poorly understood. The l-arginine metabolic system has been implicated in changes in the brain associated with aging. In the current study, we examined the levels of l-arginine and its metabolizing enzymes and downstream metabolites in the vestibular nucleus complex (VNC) and cerebellum (CE) of rats with and without behavioral testing which were young (4months old), middle-aged (12months old) or aged (24months old). We found that aging was associated with lower nitric oxide synthase activity in the CE of animals with testing and increased arginase in the VNC and CE of animals with testing. l-citrulline and l-ornithine were lower in the VNC of aged animals irrespective of testing, while l-arginine and l-citrulline were lower in the CE with and without testing, respectively. In the VNC and CE, aging was associated with lower levels of glutamate in the VNC, irrespective of testing. In the VNC it was associated with higher levels of agmatine and putrescine, irrespective of testing. In the CE, aging was associated with higher levels of putrescine in animals without testing and with higher levels of spermine in animals with testing, and spermidine, irrespective of testing. Multivariate analyses indicated significant predictive relationships between the different variables, and there were correlations between some of the neurochemical variables and behavioral measurements. Cluster analyses revealed that aging altered the relationships between l-arginine and its metabolites. The results of this study demonstrate that there are major changes occurring in l-arginine metabolism in the VNC and CE as a result of age, as well as behavioral activity. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Dienogest in long-term treatment of endometriosis

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Schindler AE

2011-07-01

Full Text Available Adolf E SchindlerInstitute for Medical Research and Education, Essen, GermanyAbstract: Endometriosis is a chronic disease primarily affecting women of childbearing age, in which endometriotic lesions form outside the uterus, typically leading to painful symptoms, fatigue, and infertility. The symptoms of endometriosis may cause significant impairment in quality of life and represent a substantial economic burden to patients, families, and society. There is no cure for endometriosis; management consists of alleviating pain and other symptoms, reducing endometriotic lesions, and improving quality of life. Recurrence after surgical intervention is common, while the clinical evidence to support the efficacy and safety of many medications currently used in endometriosis is limited. Dienogest is an oral progestin that has been investigated extensively in the treatment of endometriosis in two clinical programs performed in Europe and Japan, including dose-ranging, placebo-controlled, active comparator-controlled, and long-term (up to 65 weeks studies. These studies demonstrated that dienogest 2 mg daily effectively alleviates the painful symptoms of endometriosis, reduces endometriotic lesions, and improves indices of quality of life. Dienogest showed a favorable safety and tolerability profile in these studies, with predictable adverse effects, high rates of patient compliance, and low withdrawal rates. This review article describes the clinical trial evidence that characterizes the efficacy and safety of dienogest in endometriosis, including two studies characterizing dienogest in long-term use. The relevance of these findings to the management of endometriosis in clinical practice is discussed.Keywords: dienogest, endometriosis, progestins, long-term treatment, quality of life, symptoms, pain

Long-term selection experiment with Afrikaner cattle

African Journals Online (AJOL)

Mario Beffa

Long-term selection experiment with Afrikaner cattle. 3. Selection applied and response in calf growth traits. L.M. Beffa. 1,2,3. , J.B. van Wyk. 1# and G.J. Erasmus. 1. 1 University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa. 2 Matopos Research Station, P. Bag K5137, Bulawayo, Zimbabwe ...

Recovery and Stability of Δ9-Tetrahydrocannabinol Using the Oral-Eze® Oral Fluid Collection System and Intercept® Oral Specimen Collection Device.

Science.gov (United States)

Samano, Kimberly L; Anne, Lakshmi; Johnson, Ted; Tang, Kenneth; Sample, R H Barry

2015-10-01

Oral fluid (OF) is increasingly used for clinical, forensic and workplace drug testing as an alternative to urine. Uncertainties surrounding OF collection device performance, drug stability and testing reproducibility may be partially responsible for delays in the implementation of OF testing in regulated drug testing programs. Stability of Δ(9)-tetrahydrocannabinol (THC) fortified and authentic specimens was examined after routine collection, transport and laboratory testing. Acceptable recovery and stability were observed when THC-fortified OF (1.5 and 4.5 ng/mL) was applied to Oral-Eze devices. Neat OF samples collected with Oral-Eze, processed per the package insert, and fortified with THC (3 and 6 ng/mL) were stable (±20%) at room temperature (21-25°C), refrigerated (2-8°C) and frozen (-25 to -15°C) conditions up to 1 month, while samples collected with Intercept devices showed decreases at refrigerated and room temperatures. After long-term refrigerated or frozen storage, maximum reductions in THC concentrations were 42% for Oral-Eze and 69% for Intercept. After ≥1 year frozen storage, 80.7% of laboratory specimens positive for THC (3 ng/mL cut-off) by GC-MS were reconfirmed positive (within 25%), with an average THC decrease of 4.2%. Specimens (n = 47) processed with Oral-Eze (diluted) and tested via enzyme immunoassay were concordant with LC-MS-MS results and showed 100% sensitivity and 95% specificity. Paired specimens collected with Oral-Eze and Intercept exhibited 98% overall agreement between the immunoassay test systems. Collectively, these data demonstrate consistent and reproducible recovery and stability of THC in OF after collection, transport and laboratory testing using the Oral-Eze OF Collection System. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The pharmacokinetics of L-tryptophan following its intravenous and oral administration.

OpenAIRE

Green, A R; Aronson, J K; Cowen, P J

1985-01-01

The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The data obtained following the oral administration of L-tryptophan suggest that the total body clearance and apparent volume of distribution are saturable. The pharmacokinetics of tr...

Amniotic Fluid Arginine from Gestational Weeks 13 to 15 Is a Predictor of Birth Weight, Length, and Head Circumference

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Astrid Bjørke-Jenssen

2017-12-01

Full Text Available Arginine is a constituent of proteins and a precursor for polyamines and nitric oxide, and is essential for placentation, angiogenesis, and growth. Maternal plasma arginine concentrations are found to be lower in pregnancies complicated by fetal growth restriction, and arginine supplementation in later pregnancy is reported to increase birth weight. We measured arginine and the metabolites asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA in the amniotic fluid obtained in pregnancy weeks 13 to 15 from 363 pregnancies with a documented normal outcome and related the concentrations to birth weight, length, and head circumference. Arginine was higher in the amniotic fluid from female (mean 40.8 (SD 10.6 µmol/L compared to male fetuses (37.4 (SD 11.2 µmol/L, p = 0.003. Despite the gender difference, arginine in the amniotic fluid from gestational weeks 13–15 was the strongest predictor for birth weight, length, and head circumference. ADMA was a strong predictor for birth weight and length, SDMA for birth weight, while Arg/ADMA and Arg/SDMA only predicted head circumference in multiple linear regression models. Due to increased arginine demands, pregnancy is considered a state of relative arginine deficiency. Our findings reflect the importance of a good maternal arginine status in early pregnancy, an observation that should be evaluated in an intervention study.

Long-term continuous N-carbamylglutamate treatment in frequently decompensated propionic acidemia: a case report.

Science.gov (United States)

Tummolo, Albina; Melpignano, Livio; Carella, Antonella; Di Mauro, Anna Maria; Piccinno, Elvira; Vendemiale, Marcella; Ortolani, Federica; Fedele, Stefania; Masciopinto, Maristella; Papadia, Francesco

2018-04-22

Propionic acidemia is a rare autosomal recessive inherited metabolic disorder that can inhibit the synthesis of N-acetylglutamate, the obligatory activator in urea synthesis, leading to hyperammonemia. N-carbamylglutamate ameliorates hyperammonemia in decompensated propionic acidemia. The effects of long-term continuous N-acetylglutamate administration in such patients are unknown. We report our clinical experience with continuous administration of N-acetylglutamate for 6 years in a patient with propionic acidemia frequently presenting with hyperammonemia. A male Caucasian patient with frequently decompensated propionic acidemia and hyperammonemia was admitted 78 times for acute attacks during the first 9 years of his life. Continuous daily treatment with oral N-carbamylglutamate 100 mg/kg (50 mg/kg after 6 months) was initiated. During 6 years of treatment, he had a significant decrease in his mean plasma ammonia levels (75.7 μmol/L vs. 140.3 μmol/L before N-carbamylglutamate therapy, p N-acetylglutamate administration outside the emergency setting. If this observation is confirmed, future studies should aim to optimize the dosage and explore effects of the dosage requirements on other drugs and on protein tolerance.

Sensitive radioimmunoassay for plasma arginine vasopressin

International Nuclear Information System (INIS)

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

1980-01-01

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

Endothelial arginine resynthesis contributes to the maintenance of vasomotor function in male diabetic mice.

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Ramesh Chennupati

Full Text Available Argininosuccinate synthetase (ASS is essential for recycling L-citrulline, the by-product of NO synthase (NOS, to the NOS substrate L-arginine. Here, we assessed whether disturbed arginine resynthesis modulates endothelium-dependent vasodilatation in normal and diabetic male mice.Endothelium-selective Ass-deficient mice (Assfl/fl/Tie2Cretg/- = Ass-KOTie2 were generated by crossing Assfl/fl mice ( = control with Tie2Cre mice. Gene ablation in endothelial cells was confirmed by immunohistochemistry. Blood pressure (MAP was recorded in 34-week-old male mice. Vasomotor responses were studied in isolated saphenous arteries of 12- and 34-week-old Ass-KOTie2 and control animals. At the age of 10 weeks, diabetes was induced in control and Ass-KOTie2 mice by streptozotocin injections. Vasomotor responses of diabetic animals were studied 10 weeks later. MAP was similar in control and Ass-KOTie2 mice. Depletion of circulating L-arginine by arginase 1 infusion or inhibition of NOS activity with L-NAME resulted in an increased MAP (10 and 30 mmHg, respectively in control and Ass-KOTie2 mice. Optimal arterial diameter, contractile responses to phenylephrine, and relaxing responses to acetylcholine and sodium nitroprusside were similar in healthy control and Ass-KOTie2 mice. However, in diabetic Ass-KOTie2 mice, relaxation responses to acetylcholine and endothelium-derived NO (EDNO were significantly reduced when compared to diabetic control mice.Absence of endothelial citrulline recycling to arginine did not affect blood pressure and systemic arterial vasomotor responses in healthy mice. EDNO-mediated vasodilatation was significantly more impaired in diabetic Ass-KOTie2 than in control mice demonstrating that endothelial arginine recycling becomes a limiting endothelial function in diabetes.

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)

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

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Vannevel, Valerie; Claes, Kathleen; Baud, David; Vial, Yvan; Golshayan, Delaviz; Yoon, Eugene W; Hodges, Ryan; Le Nepveu, Anne; Kerr, Peter G; Kennedy, Claire; Higgins, Mary; Resch, Elisabeth; Klaritsch, Philipp; Van Mieghem, Tim

2018-01-01

Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term. We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed. We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65). Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

Persistent negative illness perceptions despite long-term biochemical control of acromegaly: novel application of the drawing test.

Science.gov (United States)

Tiemensma, Jitske; Pereira, Alberto M; Romijn, Johannes A; Broadbent, Elizabeth; Biermasz, Nienke R; Kaptein, Adrian A

2015-05-01

Patients with acromegaly have persistent complaints despite long-term biochemical control. Drawings can be used to assess patients' perceptions about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions and quality of life (QoL) in patients after long-term remission of acromegaly. A cross-sectional study was conducted to evaluate the utility of the drawing test. A total of 50 patients after long-term remission (mean±s.e.m., 16±1.2 years) of acromegaly were included in this study. Patients completed the drawing test (two retrospective drawings of their body perception before acromegaly and during the active phase of acromegaly, and one drawing on the current condition after long-term remission), Illness Perception Questionnaire-Revised, Physical Symptom Checklist, EuroQoL-5D, and AcroQoL. Patients perceived a dramatic change in body size during the active state of the disease compared with the healthy state before the awareness of acromegaly. Patients reported that their body did not completely return to the original proportions after long-term remission. In addition, larger drawings indicated more negative consequences (Pdrawings also indicated more impaired QoL, especially disease-specific QoL (all Pdrawing test, illness perceptions, and QoL. The drawing test appears to be a novel and relatively easy tool to assess the perception of patients after long-term remission of acromegaly. The assessment of drawings may enable health care providers to appreciate the perceptions of patients with long-term remission of acromegaly, and enable discussion of symptoms and remission. © 2015 European Society of Endocrinology.

Anaerobic ammonium-oxidizing bacteria gain antibiotic resistance during long-term acclimatization.

Science.gov (United States)

Zhang, Zheng-Zhe; Zhang, Qian-Qian; Guo, Qiong; Chen, Qian-Qian; Jiang, Xiao-Yan; Jin, Ren-Cun

2015-09-01

Three broad-spectrum antibiotics, amoxicillin (AMX), florfenicol (FF) and sulfamethazine (SMZ), that inhibit bacteria via different target sites, were selected to evaluate the acute toxicity and long-term effects on anaerobic ammonium oxidation (anammox) granules. The specific anammox activity (SAA) levels reduced by approximately half within the first 3 days in the presence of antibiotics but no nitrite accumulation was observed in continuous-flow experiments. However, the SAA levels and heme c content gradually recovered as the antibiotic concentrations increased. Extracellular polymeric substances (EPS) analysis suggested that anaerobic ammonium-oxidizing bacteria gradually developed a better survival strategy during long-term acclimatization, which reduced the antibiotic stress via increased EPS secretion that provided a protective 'cocoon.' In terms of nitrogen removal efficiency, anammox granules could resist 60 mg-AMX L(-1), 10 mg-FF L(-1) and 100 mg-SMZ L(-1). This study supported the feasibility of using anammox granules to treat antibiotic-containing wastewater. Copyright © 2015 Elsevier Ltd. All rights reserved.

Long-term safety of the maintenance and decommissioning waste of the encapsulation plant

International Nuclear Information System (INIS)

Nummi, O.; Kylloenen, J.; Eurajoki, T.

2012-12-01

This report, Long-term safety of the maintenance and decommissioning waste of the encapsulation plant, presents the disposal concept for the low and intermediate level waste (L/ILW) that is generated during the operation and decommissioning of the encapsulation plant, and assesses the long-term safety of the disposal of the waste. Radioactive waste originates from the spent nuclear fuel transferred and dried in the encapsulation plant. Radioactive waste accumulates also in the maintenance of the components and systems of the encapsulation plant. The waste is collected, exempted from control if possible and treated for final disposal if necessary. The waste is disposed of in the L/ILW hall which is currently planned to be located at a depth of -180 meters along the access tunnel to the repository for spent fuel. The main engineered barrier in the L/ILW hall is a concrete basin that encases the dried liquid waste. The safety concept of L/ILW disposal is based on the slow release of radioactivity from the L/ILW hall and its limited transport through the bedrock into biosphere. The release and transport of the radioactivity is described by the assessment scenarios, which include expected evolution and unlikely events affecting the long-term safety. The scenarios act as guidelines according to which the conceptual and mathematical models are formed. The long-term safety of the L/ILW hall is assessed using deterministic and probabilistic modeling. Special issues such as human intrusion and radiation effects on other biota are also assessed. The most significant contributor to the dose rates is the short-lived radionuclide 90 Sr followed by long-lived nuclides 129 I and 108 mAg. The annual doses to the public, and release rates of radioactive substances stay below the regulatory constraints in all analyzed scenarios. (orig.)

[Long-term psychiatric hospitalizations].

Science.gov (United States)

Plancke, L; Amariei, A

2017-02-01

Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

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Sun Yuan

2006-02-01

Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

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.

Long-term potentiation and olfactory memory formation in the carp (Cyprinus carpio L.) olfactory bulb.

Science.gov (United States)

Satou, M; Anzai, S; Huruno, M

2005-05-01

Long-term potentiation of synaptic transmission is considered to be an elementary process underlying the cellular mechanism of memory formation. In the present study we aimed to examine whether or not the dendrodendritic mitral-to-granule cell synapses in the carp olfactory bulb show plastic changes after their repeated activation. It was found that: (1) the dendrodendritic mitral-to-granule cell synapses showed three types of plasticity after tetanic electrical stimulation applied to the olfactory tract-long-term potentiation (potentiation lasting >1 h), short-term potentiation (potentiation lasting 1 h) of the odor-evoked bulbar response accompanied the electrically-induced LTP, and; (4) repeated olfactory stimulation enhanced dendrodendritic mitral-to-granule cell transmission. Based on these results, it was proposed that long-term potentiation (as well as olfactory memory) occurs at the dendrodendritic mitral-to-granule cell synapses after strong and long-lasting depolarization of granule cells, which follows repeated and simultaneous synaptic activation of both the peripheral and deep dendrites (or somata).

Dissecting rice polyamine metabolism under controlled long-term drought stress.

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Phuc Thi Do

Full Text Available A selection of 21 rice cultivars (Oryza sativa L. ssp. indica and japonica was characterized under moderate long-term drought stress by comprehensive physiological analyses and determination of the contents of polyamines and selected metabolites directly related to polyamine metabolism. To investigate the potential regulation of polyamine biosynthesis at the transcriptional level, the expression of 21 genes encoding enzymes involved in these pathways were analyzed by qRT-PCR. Analysis of the genomic loci revealed that 11 of these genes were located in drought-related QTL regions, in agreement with a proposed role of polyamine metabolism in rice drought tolerance. The cultivars differed widely in their drought tolerance and parameters such as biomass and photosynthetic quantum yield were significantly affected by drought treatment. Under optimal irrigation free putrescine was the predominant polyamine followed by free spermidine and spermine. When exposed to drought putrescine levels decreased markedly and spermine became predominant in all cultivars. There were no correlations between polyamine contents and drought tolerance. GC-MS analysis revealed drought-induced changes of the levels of ornithine/arginine (substrate, substrates of polyamine synthesis, proline, product of a competing pathway and GABA, a potential degradation product. Gene expression analysis indicated that ADC-dependent polyamine biosynthesis responded much more strongly to drought than the ODC-dependent pathway. Nevertheless the fold change in transcript abundance of ODC1 under drought stress was linearly correlated with the drought tolerance of the cultivars. Combining metabolite and gene expression data, we propose a model of the coordinate adjustment of polyamine biosynthesis for the accumulation of spermine under drought conditions.

Study on thermostabilizers for trivalent oral poliomyelitis vaccine

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M. L. F. Leal

1990-09-01

Full Text Available Different formulations of trivalent oral poliomyelitis vaccine were tested, in order to obtain better thermostability, reduce corrosion of machinery and improve production costs. Magnesium chloride, sucrose, arginine and 199-Hank's medium were used in the formulations. The most appropriate formulation was a mixture of MgCl2 and arginine, which was highly thermostable, and had low production costs. The low corrosive formulation was rejected, due to low thermostability on storage.

Factors affecting long-term integrity of transmission pipelines; Facteurs affectant l'integrite a long terme des gazoducs

Energy Technology Data Exchange (ETDEWEB)

Hagiwara, N.; Masuda, T.; Oguchi, N. [Tokyo Gas Co., Ltd. (Japan)

2000-07-01

For upgrading long-term integrity of transmission pipelines, two types of delayed fracture in regions of mechanical damage in pipelines were investigated. Experimental and numerical studies clarified factors affecting the fatigue behavior of line pipes containing an idealized flaw under fluctuating internal pressure. To investigate fatigue cracking at mechanical damage in pipelines, degradation of fracture toughness and fatigue properties due to plastic pre-strain was also evaluated. A fracture mechanics-based study revealed conditions necessarily for initiation of hydrogen stress cracking (HSC) at a surface defect in line pipes under cathodic protection. (authors)

Long-term potentiation and long-term depression: a clinical perspective

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Timothy V.P. Bliss

2011-01-01

Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Science.gov (United States)

Favaro, Vanessa Manchim; Yonamine, Maurício; Soares, Juliana Carlota Kramer; Oliveira, Maria Gabriela Menezes

2015-01-01

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats.

Directory of Open Access Journals (Sweden)

Vanessa Manchim Favaro

Full Text Available Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM, fear conditioning and elevated plus maze (EPM performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Effect of aliskiren, telmisartan and torsemide on cardiac dysfunction in l-nitro arginine methyl ester (l-NAME induced hypertension in rats

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Sawsan A. Sadek

2015-11-01

Full Text Available Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2−/NO3−. After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure.

ORAL CLINICAL LONG CASE PRESENTATION, THE NEED FOR STANDARDIZATION AND DOCUMENTATION.

Science.gov (United States)

Agodirin, S O; Olatoke, S A; Rahman, G A; Agbakwuru, E A; Kolawole, O A

2015-01-01

The oral presentation of the clinical long case is commonly an implied knowledge. The challenge of the presentation is compounded by the examiners' preferences and sometimes inadequate understanding of what should be assessed. To highlight the different opinions and misconceptions of trainers as the basis for improving our understanding and assessment of oral presentation of the clinical long case. Questionnaire was administered during the West African College of Surgeons fellowship clinical examinations and at their workplaces. Eligibility criteria included being a surgeon, a trainer and responding to all questions. Of the 72 questionnaires that were returned, 36(50%) were eligible for the analysis. The 36 respondents were from 14 centers in Nigeria and Ghana. Fifty-two percent were examiners at the postgraduate medical colleges and 9(25%) were professors. Eight(22.2%) indicated they were unaware of the separate methods of oral presentation for different occasions while 21( 58.3%) respondents were aware that candidate used the "5Cs" method and the traditional compartmentalized method in long case oral presentation. Eleven(30.6%) wanted postgraduates to present differently on a much higher level than undergraduate despite not encountering same in literature and 21(58.3%) indicated it was an unwritten rule. Seventeen (47.2%) had not previously encountered the "5Cs" of history of presenting complaint in literature also 17(47.2%) teach it to medical students and their junior residents. This study has shown that examiners definitely have varying opinions on what form the oral presentation of the clinical long case at surgery fellowship/professional examination should be and it translates to their expectations of the residents or clinical students. This highlights the need for standardization and consensus of what is expected at a formal oral presentation during the clinical long case examination in order to avoid subjectivity and bias.

Esophageal replacement in children: Challenges and long-term outcomes

Directory of Open Access Journals (Sweden)

Giampiero Soccorso

2016-01-01

Full Text Available Replacement of a nonexistent or damaged esophagus continues to pose a significant challenge to pediatric surgeons. Various esophageal replacement grafts and techniques have not produced consistently good outcomes to emulate normal esophagus. Therefore, many techniques are still being practiced and recommended with no clear consensus. We present a concise literature review of the currently used techniques and with discussions on the advantages and anticipated morbidity. There are no randomized controlled pediatric studies to compare different types of esophageal replacements. Management and graft choice are based on geographical and personal predilections rather than on any discernible objective data. The biggest series with long-term outcome are reported for gastric transposition and colonic replacement. Comparison of different studies shows no significant difference in early (graft necrosis and anastomotic leaks or late complications (strictures, poor feeding, gastro-esophageal reflux, tortuosity of the graft, and Barrett′s esophagus. The biggest series seem to have lower complications than small series reflecting the decennials experience in their respective centers. Long-term follow-up is recommended following esophageal replacement for the development of late strictures, excessive tortuosity, and Barrett′s changes within the graft. Once child overcomes initial morbidity and establishes oral feeding, long-term consequences and complications of pediatric esophageal replacement should be monitored and managed in adult life.

Conditioning radium needles for long term storage : Sri Lankan experience

International Nuclear Information System (INIS)

Ranjith, H.L.A.; Shantha, T.H.S.; Gunaratne, M.G.J.; De Silva, U.W.K.H.; Perera, H.P.H.

2000-01-01

Radium the first radioisotope invented by Madame Curie was used for cancer therapy for the intracavitory treatment of cervical cancers and as oral implants etc. Radium needles and other geometries were made in standard strengths and Radium therapy enjoyed a heyday during the 1st half of the 20th century. Radium-226 is a long-lived radioactive material with a half-life of 1600 years. The use of radium was abandoned in the world in 1980s with the invention of short lived radioactive materials offering remote after loading systems which minimise radiation protection and waste disposal problems associated with long lived radioactive materials. This paper reports the conditioning procedure of the spent radium sources for long term storage (less than 20 years) and transport to national/ international stores if needed. The dose received by those involved in this exercise is also discussed in terms of radiation protection. The Ra was contained for long term storage according to international radiation safety regulations with a surface dose of less than 2 mSv per hour in a conditioned package having 17.5 GBq activity and can be transported to national/international stores if needed. The highest dose received during the exercise is well within the recommended dose limits for occupational exposures (20 and 500 mSv per year) for whole body and extremities respectively

Immediate perception of a reward is distinct from the reward’s long-term salience

Science.gov (United States)

McGinnis, John P; Jiang, Huoqing; Agha, Moutaz Ali; Sanchez, Consuelo Perez; Lange, Jeff; Yu, Zulin; Marion-Poll, Frederic; Si, Kausik

2016-01-01

Reward perception guides all aspects of animal behavior. However, the relationship between the perceived value of a reward, the latent value of a reward, and the behavioral response remains unclear. Here we report that, given a choice between two sweet and chemically similar sugars—L- and D-arabinose—Drosophila melanogaster prefers D- over L- arabinose, but forms long-term memories of L-arabinose more reliably. Behavioral assays indicate that L-arabinose-generated memories require sugar receptor Gr43a, and calcium imaging and electrophysiological recordings indicate that L- and D-arabinose differentially activate Gr43a-expressing neurons. We posit that the immediate valence of a reward is not always predictive of the long-term reinforcement value of that reward, and that a subset of sugar-sensing neurons may generate distinct representations of similar sugars, allowing for rapid assessment of the salient features of various sugar rewards and generation of reward-specific behaviors. However, how sensory neurons communicate information about L-arabinose quality and concentration—features relevant for long-term memory—remains unknown. DOI: http://dx.doi.org/10.7554/eLife.22283.001 PMID:28005005

Evidence for arginine as the endogenous precursor of necines in heliotropium.

Science.gov (United States)

Birecka, H; Birecki, M; Frohlich, M W

1987-05-01

In pyrrolizidine alkaloid-bearing Heliotropium angiospermum and H. indicum shoots exposed, in the light, to (14)C-labeled CO(2) for 44 hours, the incorporation of (14)C into 1,2-epoxy-1-hydroxymethylpyrrolizidine and retronecine amounted to 0.23 and 0.15%, respectively, of the total carbon assimilated. Treatment of the shoots with alpha-dl-difluoromethylornithine, the specific ornithine decarboxylase inhibitor, at 1 to 2 millimolar had no effect on (14)C incorporation into the necines. In contrast, alpha-dl-difluoromethylarginine, the specific arginine decarboxylase inhibitor, prevented the incorporation of (14)C into the necines of both species; the inhibitor did not affect the absolute incorporation of (14)C from exogenous [1,4-(14)C] putrescine in either species. Thus, arginine is the only apparent endogenous precursor of the putrescine channeled into pyrrolizidines, at least in these two Heliotropium species that exhibited a relatively much higher in vitro activity of arginine decarboxylase than of ornithine decarboxylase. However, within 28 hours after administration, not only exogenous l-[5-(14)C]arginine, but also exogenous l-[5-(14)C]ornithine exhibited significant incorporation of their label into the necines, incorporation that could be partially prevented by both inhibitors. Neither inhibitor affected the rates of (14)C-labeled CO(2) assimilation, transformation of labeled assimilates into ethanol-insoluble compounds, or the very high degree of conversion of the introduced amino acids into other compounds. Methodology related to alkaloid biosynthetic studies is discussed.

Antimetastatic effects of Rheum palmatum L. extract on oral cancer cells.

Science.gov (United States)

Chen, Yang-Yu; Hsieh, Ming-Ju; Hsieh, Yih-Shou; Chang, Yu-Chao; Chen, Pei-Ni; Yang, Shun-Fa; Ho, Hsin-Yu; Chou, Ying-Erh; Lin, Chiao-Wen

2017-10-01

Rheum palmatum L., a traditional Chinese medication, has been used for the treatment of various disorders. However, the detailed impacts and underlying mechanisms of R. palmatum L. extracts (RLEs) on human oral cancer cell metastasis are still unclear. Here, we tested the hypothesis that an RLE has antimetastatic effects on SCC-9 and SAS human oral cancer cells. Gelatin zymography, Western blot, real-time polymerase chain reaction, and luciferase assay were used to explore the underlying mechanisms involved in the antimetastatic effects on oral cancer cells. Our results revealed that the RLE (up to 20 μg/mL, without cytotoxicity) attenuated SCC-9 and SAS cell motility, invasiveness, and migration by reducing matrix metalloproteinase (MMP)-2 enzyme activities. Western blot analysis of the MAPK signaling pathway indicated that the RLE significantly decreased phosphorylated ERK1/2 levels but not p38 and JNK levels. In conclusion, RLEs exhibit antimetastatic activity against oral cancer cells through the transcriptional repression of MMP-2 via the Erk1/2 signaling pathways. Thus, RLEs may be potentially useful as antimetastatic agents for oral cancer chemotherapy. © 2017 Wiley Periodicals, Inc.

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

Energy Technology Data Exchange (ETDEWEB)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia [Department of Imaging, Interventional Radiology, and Nuclear Medicine, Diakonissen Hospital, Diakonissenstrasse 28, 76199, Karlsruhe (Germany)

2004-02-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76{+-}7.5% (1 year), and 70{+-}9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75{+-}4.6% (1 year), and 50{+-}8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87{+-}5.8% (1 year), and 72{+-}9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

International Nuclear Information System (INIS)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia

2004-01-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76±7.5% (1 year), and 70±9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75±4.6% (1 year), and 50±8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87±5.8% (1 year), and 72±9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with CLAFS

Metabolism of 14C-L-arginine and 14C-L-proline in excised burst buds and stem sections of citrus trees (Citrus unshiu Marc.)

International Nuclear Information System (INIS)

Kato, Tadashi; Yamagata, Makoto; Tsukahara, Sadao

1985-01-01

Arginine and proline, which are the major forms of soluble reserve N, were fed singly in uniformly labelled 14 C-form to excised 2-year-old stem sections with a new shoot, to wood sections, and to burst buds from a 21-year-old satsuma mandarin tree. Metabolism was studied by radioassay and autoradiography. In stem sections with a new shoot, both 14 C-compounds were metabolized to acidic and neutral components, insoluble components, and 14 CO 2 . This conversion occurred to a greater extent in sections fed with arginine than with proline. When 14 C-arginine was fed, the highest 14 C-activity in the cationic fraction of stem sections, bark, wood and new shoots was found in γ-guanidinobutyric acid, followed by γ-aminobutyric acid and proline; low levels of 14 C was also found in ornithine and trace amounts in citrulline. These findings demonstrate that arginine is metabolized by at least two routes: via ornithine and via γ-guanidinobutyric acid. In every organ, the major metabolic products of 14 C-proline were pyrrolidone-5-carboxlic acid, glutamic acid, aspartic acid, asparagine, an unidentified compound (U 5 in Fig. 4), γ-aminobutyric acid and arginine. The basic metabolic pathways in the conversion of Both 14 C-compounds were the same in burst buds, new shoot, bark and wood, although there was a slight difference autoradiographically. (author)

Transcriptome analysis shows activation of the arginine deiminase pathway in Lactococcus lactis as a response to ethanol stress.

Science.gov (United States)

Díez, Lorena; Solopova, Ana; Fernández-Pérez, Rocío; González, Miriam; Tenorio, Carmen; Kuipers, Oscar P; Ruiz-Larrea, Fernanda

2017-09-18

This paper describes the molecular response of Lactococcus lactis NZ9700 to ethanol. This strain is a well-known nisin producer and a lactic acid bacteria (LAB) model strain. Global transcriptome profiling using DNA microarrays demonstrated a bacterial adaptive response to the presence of 2% ethanol in the culture broth and differential expression of 67 genes. The highest up-regulation was detected for those genes involved in arginine degradation through the arginine deiminase (ADI) pathway (20-40 fold up-regulation). The metabolic responses to ethanol of wild type L. lactis strains were studied and compared to those of regulator-deletion mutants MG∆argR and MG∆ahrC. The results showed that in the presence of 2% ethanol those strains with an active ADI pathway reached higher growth rates when arginine was available in the culture broth than in absence of arginine. In a chemically defined medium strains with an active ADI pathway consumed arginine and produced ornithine in the presence of 2% ethanol, hence corroborating that arginine catabolism is involved in the bacterial response to ethanol. This is the first study of the L. lactis response to ethanol stress to demonstrate the relevance of arginine catabolism for bacterial adaptation and survival in an ethanol containing medium. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency

Science.gov (United States)

2012-01-01

Background SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain–blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. Methods In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300 mg/kg/day divided into 3 doses, for 24–36 months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. Results During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. Conclusion This study provides information to support the effectiveness of L-Arg supplement treatment in

Long-Term Symbolic Learning

National Research Council Canada - National Science Library

Kennedy, William G; Trafton, J. G

2007-01-01

What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

Pediatric polytrauma : Short-term and long-term outcomes

NARCIS (Netherlands)

vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

Dietary arginine and linear growth

DEFF Research Database (Denmark)

van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W

2013-01-01

Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept......The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School...... and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity...

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs.

Science.gov (United States)

Luna, Stelio P L; Basílio, Ana C; Steagall, Paulo V M; Machado, Luciana P; Moutinho, Flávia Q; Takahira, Regina K; Brandão, Cláudia V S

2007-03-01

To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. 36 adult dogs. Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Haloperidol for long-term aggression in psychosis.

Science.gov (United States)

Khushu, Abha; Powney, Melanie J

2016-11-27

Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

Long-term surgical-orthodontic management of hemimandibular hyperplasia.

Science.gov (United States)

Bennett, Samuel C; Goonewardene, Mithran S

2016-05-01

Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical unilateral elongation of the mandible becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and the dental compensatory mechanism is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is effectively managed by combined surgical-orthodontic care to address the facial, skeletal and dental problems that confront clinicians. Orthodontists are advised to assess patients with HH during the post-treatment retention stage for continuing mandibular growth and assess the stability of treatment outcomes with long-term follow-up and records as required. To present a case of hemimandibular hyperplasia treated successfully by combined surgical-orthodontic care and evaluated for stability over a seven-year follow-up period. Surgical-orthodontic management was accomplished in four stages: 1) pre-surgical orthodontic; 21 surgical; 3) post-surgical orthodontic; and 4) post-treatment orthodontic retention. Complete orthodontic records, including extra- and intra-oral photographs, study models, and cephalograms plus panoramic radiographs were taken at the pretreatment, post-treatment, and seven-year orthodontic retention time-points. Facial, skeletal and dental goals were achieved in the three planes of space and the long-term stability of the treatment results was shown during a post-treatment orthodontic retention period of seven years. Hemimandibular hyperplasia is a true growth anomaly which may be managed effectively. Clinicians may expect successful long-term correction and stability by utilising a comprehensive surgical-orthodontic treatment approach.

IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

Directory of Open Access Journals (Sweden)

E. A. Starikova

2015-01-01

Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

Supplementing a commercial diet for atlantic salmon (Salmo salar L.) with arginine, glutamate or tetradecylthioacetic acid (TTA). impact on production efficiency, slaughter parameters and flesh quality

OpenAIRE

Rahnama, Behzad

2010-01-01

The present study was carried out to evaluate the effects of supplementing a commercial diets with 1.5% L-arginine, 1.5% L-glutamate or 0.25% tetradecylthioacetic acid (TTA) on feed intake, feed utilization and growth parameters of Atlantic salmon (Salmo salar L.) during the critical periods after sea transfer with regard to seawater adaptation and onwards, from April to September. In the case of TTA, fish were fed until they reached a weight gain of 0.2% of the initial body weight, thereafte...

The control of fruiting body formation in the ascomycete Sordaria macrospora Auersw. by arginine and biotin: a two-factor analysis.

Science.gov (United States)

Molowitz, R; Bahn, M; Hock, B

1976-01-01

Fruiting body formation of Sordaria macrospora Auersw. is controlled by L-arginine and biotin when the fungus is grown on a synthetic nutrient medium containing optimal concentrations of fructose, KNO3, KH2PO4, MgSO4, and ZnSO4. Arginine and biotin operate in very low concentrations which exclude unspecific nutrient effects. In spite of the complicated interactions of arginine and biotin which are shown qualitatively (Figs. 3 and 4a) and quantitatively (Figs. 2 and 4b), the following conclusions are reached: 1. In the absence of biotin, the development of Sordaria macrospora is blocked at the stage of small protoperithecia. The external addition of biotin (optimal concentration: 3-12 μg/l) allows the formation of fertile fruiting bodies. This effect cannot be imitated by arginine. The biotin effect is discussed in connection with stimulated RNA synthesis.-2. The developmental velocity is influenced by the external addition of arginine. Without arginine but at permissible biotin concentrations, the total life cycle takes about 10 days, in the presence of arginine (1 mM), however, about 6 days.-3. The hyphal density, as well as the total number of fruiting bodies being produced, is controlled in a similar manner by biotin and arginine. The induction of fruiting body formation obviously takes place after the transgression of a critical hyphal density.

Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice

Science.gov (United States)

Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depl...

Neurocognitive function in clinically stable individuals with long-term bipolar I disorder: Comparisons with schizophrenia patients and controls

Directory of Open Access Journals (Sweden)

Pei-Yun Lin

2017-05-01

Full Text Available This study compared the levels of the five domains of neurocognitive function—executive function, attention, memory, verbal comprehension, and perceptual organization—among clinically stable individuals with long-term bipolar I disorder, individuals with long-term schizophrenia, and a group of controls. We recruited a total of 93 clinically stable individuals with bipolar I disorder, 94 individuals with schizophrenia, and 106 controls in this study. Their neurocognitive function was measured using a series of neurocognitive function tests: the Wechsler Adult Intelligence Scale—Third Edition (WAIS-III, Line Cancellation Test, Visual Form Discrimination, Controlled Oral Word Association Test, Wisconsin Card Sorting Test, Continuous Performance Task, and Wechsler Memory Scale—Third Edition. Neurocognitive function was compared among the three groups through a multivariate analysis of variance. The results indicated that when the effect of age was controlled, clinically stable individuals with bipolar I disorder and those with schizophrenia demonstrated poor neurocognitive function on all tests except for the WAIS-III Similarity and Information and the Line Cancellation Test. The individuals with bipolar I disorder had similar levels of neurocognitive function compared with the schizophrenia group, but higher levels of neurocognitive function on the WAIS-III Comprehension, Controlled Oral Word Association Test, and Wechsler Memory Scale—Third Edition Auditory Immediate and Delayed Index and Visual Immediate and Delayed Index. The conclusions of this study suggest that compared with controls, individuals with long-term bipolar I disorder and those with long-term schizophrenia have poorer neurocognitive function, even when clinically stable. Individuals with long-term bipolar I disorder and those with long-term schizophrenia have similar levels of deficits in several domains of neurocognitive function.

Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation.

Science.gov (United States)

El-Hattab, Ayman W; Emrick, Lisa T; Hsu, Jean W; Chanprasert, Sirisak; Almannai, Mohammed; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

2016-04-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be

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

Soil CO2 evolution: Response from arginine additions

Science.gov (United States)

Short-term response of soil C mineralization following drying/rewetting has been proposed as an indicator of soil microbial activity. Houston Black clay was amended with four rates of arginine to vary microbial response and keep other soil properties constant. The evolution of CO2 during one and thr...

Near-Term Actions to Address Long-Term Climate Risk

Science.gov (United States)

Lempert, R. J.

2014-12-01

Addressing climate change requires effective long-term policy making, which occurs when reflecting on potential events decades or more in the future causes policy makers to choose near-term actions different than those they would otherwise pursue. Contrary to some expectations, policy makers do sometimes make such long-term decisions, but not as commonly and successfully as climate change may require. In recent years however, the new capabilities of analytic decision support tools, combined with improved understanding of cognitive and organizational behaviors, has significantly improved the methods available for organizations to manage longer-term climate risks. In particular, these tools allow decision makers to understand what near-term actions consistently contribute to achieving both short- and long-term societal goals, even in the face of deep uncertainty regarding the long-term future. This talk will describe applications of these approaches for infrastructure, water, and flood risk management planning, as well as studies of how near-term choices about policy architectures can affect long-term greenhouse gas emission reduction pathways.

Impact of heavy repeated long term pesticide applications on soil properties in a cotton agroecosystem

International Nuclear Information System (INIS)

Hussain, Altaf; Asi, Muhammad Rafique; Iqbal, Zafar; Chaudhry, Jamil Anwar

2001-01-01

A study was conducted under field conditions to investigate the effects of heavy repeated long term pesticide applications, at their recommended doses, on some biological properties in relation to the cotton agroecosystem at NIAB, Faisalabad, Pakistan. Control, test and treated soils before (BPA) and after pesticide applications (APA) were collected and analyzed at different stages of pesticide applications. The selective tests were measurements of microbial numbers, basal as well as substrate-induced respiration, nitrification, Fe-III reduction and the activities, of dehydrogenase and arginine deaminase. Endosulfan, profenophos + alphamethrin and methamidophos inhibited while monocrotophos and bifenthrin + acetamiprid enhanced the bacterial population numbers. The fungal population was depressed with endosulfan while monocrotophos, profenophos and methamidophos stimulated it. All other applied pesticides did not cause any appreciable change in total bacterial and fungal populations throughout the study period. Monocrotophos, propargite, endosulfan alone or with dimethoate and profenophos with cypermethrin or with ethion inhibited the respiration and hence affected the biomass. All other pesticides had no effect in test and treated soils compared to control soil. No pronounced inhibition or stimulation was seen in respiration after several weeks following the applications of pesticide. Endosulfan, endosulfan with dimethoate, methamidophos stimulated while profenophos + cypermethrin and bifenthrin + endosulfan inhibited the nitrification. All other pesticide applications showed similar nitrification rates in test and treated soils compared to control soil. Iron reduction capacity was stimulated by dimethoate + endosulfan and propenophos + cypermethrin and profenphos, methamidophos, propargite and diafenthiuron + profenophos reduced it. Soil dehydrogenase activity was inhibited by methamidophos, fenpropathrin, endosulfan + dimethoate and bifenthrin + ethion

ANDRA's Long-Term Memory-Preservation Program

International Nuclear Information System (INIS)

Charton, Patrick; Dumont, Jean-Noel

2012-01-01

Maintaining the memory of repositories over the long term is required not only to ensure safety and reversibility (legal requirements), but also in response to social expectations. Since 2010, ANDRA has been implementing a long-term memory preservation program to reinforce and diversify its current arrangements in that field, as well as explore opportunities to extend memory keeping over thousands of years. As a reference solution, ANDRA uses the arrangement and practices in place at its surface disposal facilities. Although at ANDRA they are well aware of the fact that the operational time of a LILW disposal corresponds more or less with the implementation time of a geological disposal, useful insights can nevertheless be gained from the experience with short-lived LILW. The reference solution implemented at the Centre de la Manche and de l'Aube includes five memorization devises, differentiating between passive and active memory keeping. There are three passive memories, consisting of copies with various degrees of information on permanent paper, and two active memories, consisting of oral transmissions under the form of events and meetings with various (local) stakeholders. For HLW, ANDRA calculates a timescale of 200 years for the total implementation of a geological disposal, and a minimum of memory of 500 years afterwards, which necessitates conservation of RK and M for 700 years in total. Permanent paper lasts 600-1000 years. ANDRA also developed a sapphire disk which can contain large amounts of records and endure 1 million years. In fact this device created more questions; the purpose is exactly to question 'solutions' that are solely based on engineering. It for instance evokes questions such as 'Which languages should we use, which graphical material should we add, how can we avoid vandalism, what meaning will future generations give to the traces we leave?' All these issues and more are being investigated under ANDRA's long term memory preservation

Long-term effect of /sup 90/Y pituitary implantation in acromegaly

Energy Technology Data Exchange (ETDEWEB)

Jadresic, A.; Jimenez, L.E.; Joplin, G.F.

1987-01-01

This report examines the long-term trends in GH levels and pituitary function in a group of 38 acromegalic patients who were selected insofar as we were able to follow them up for more than 10 years after a single dose /sup 90/Y interstitial pituitary irradiation as the sole treatment. Mean serum GH had fallen from 106 to 24 mIU/l within 3-6 months and then slowly declined to 4 mIU/l after 10 years. GH levels of less than or equal to 5 mIU/l during a 50 g oral glucose tolerance test were obtained in 8% of patients at 3-6 months and in 18% at 1 year, the cumulative percentage increasing to 53% at 10, and 76% at 14 years. The percentage of patients requiring hormone replacement therapy rose from nil pre-implant to 16% by 3-6 months, and then slowly increased to 39% by 14 years. Serial coned radiographs of the pituitary fossa were available for 32 patients. By 10 years, 16 showed thickening of the dorsum sellae and/or reduction of at least one diameter by 3 mm. Concerning symptoms, all 29 patients whose GH level fell to less than or equal to 5 mIU/l showed improvements, 22 becoming asymptomatic. Seven patients with lesser falls in GH levels (from a mean of 193 to a mean of 15 mIU/l) all improved, one becoming asymptomatic. Two showed no variation. These results show that /sup 90/Y pituitary implants have a cumulative effect over the years in inducting remission and hypopituitarism in acromegalic patients, the early decline in GH levels being swifter than from other forms of irradiation.

ANMCO Position Paper: long-term follow-up of patients with pulmonary thromboembolism.

Science.gov (United States)

D'Agostino, Carlo; Zonzin, Pietro; Enea, Iolanda; Gulizia, Michele Massimo; Ageno, Walter; Agostoni, Piergiuseppe; Azzarito, Michele; Becattini, Cecilia; Bongarzoni, Amedeo; Bux, Francesca; Casazza, Franco; Corrieri, Nicoletta; D'Alto, Michele; D'Amato, Nicola; D'Armini, Andrea Maria; De Natale, Maria Grazia; Di Minno, Giovanni; Favretto, Giuseppe; Filippi, Lucia; Grazioli, Valentina; Palareti, Gualtiero; Pesavento, Raffaele; Roncon, Loris; Scelsi, Laura; Tufano, Antonella

2017-05-01

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU. Acquired or congenital thrombophilic disorders could be identified in apparently unprovoked VTE during the FU. In other cases, an occult cancer could be discovered after a VTE. The main targets of the post-acute management are to prevent recurrence of VTE and to identify the patients who can develop a chronic thromboembolic pulmonary hypertension. Knowledge of pathophysiology and therapeutic approaches is fundamental to decide the most appropriate long-term treatment. Moreover, prognostic stratification during the FU should be constantly updated on the basis of the new evidence acquired. Currently, the cornerstone of VTE treatment is represented by both the oral and the parenteral anticoagulation. Novel oral anticoagulants should be an interesting alternative in the long-term treatment.

The use of natural and archaeological analogues for understanding the long-term behavior of nuclear glasses; L'utilisation des analogues naturels et archeologiques pour la comprehension de l'evolution a long terme des verres nucleaires

Energy Technology Data Exchange (ETDEWEB)

Libourel, G.; Verney-Carron, A.; Morlok, A. [CNRS UPR2300, centre de recherches petrographiques et geochimiques (CRPG), Nancy-universite, 15, rue Notre-Dame-des-Pauvres, BP 20, 54501 Vandoeuvre-les-Nancy (France); Libourel, G. [INPL, Ecole nationale superieure de geologie (ENSG), Nancy-universite, rue du Doyen-Marcel-Roubault, BP 20, 54501 Vandoeuvre-les-Nancy (France); Gin, St. [CEA Marcoule, DEN/SECM/LCLT, 30 (France); Sterpenich, J. [G2R, CNRS-UMR 7566, Nancy-universite, BP 70239, 54506 Vandoeuvre-les-Nancy cedex (France); Michelin, A.; Neff, D.; Dillmann, Ph. [Laboratoire archeomateriaux et prevision de l' alteration LAPA/SIS2 M, CEA and CNRS, Bat 637, CEA Saclay, 91191 Gif/Yvette cedex (France); Michelin, A.; Dillmann, Ph. [LMC IRAMAT UMR5060 CNRS (France)

2011-02-15

The knowledge of the long-term behavior of nuclear waste in anticipation of ultimate disposal in a deep geological formation is of prime importance in a waste management strategy. If phenomenological models have been developed to predict the long-term behavior of these materials, validating these models remains a challenge, when considering the time scale of radioactive decay of radionuclides of environmental concern, typically 10{sup 4}-10{sup 5} yrs. Here we show how natural or archaeological analogues provide critical constraints not only on the phenomenology of glass alteration and the mechanisms involved, but also on the ability of experimental short-term data to predict long-term alteration in complex environments. (authors)

Long-term performance of a 20-L continuous flow microbial fuel cell for treatment of brewery wastewater

Science.gov (United States)

Lu, Mengqian; Chen, Shing; Babanova, Sofia; Phadke, Sujal; Salvacion, Michael; Mirhosseini, Auvid; Chan, Shirley; Carpenter, Kayla; Cortese, Rachel; Bretschger, Orianna

2017-07-01

Microbial fuel cells (MFCs) have been shown as a promising technology for wastewater treatment. Integration of MFCs into current wastewater treatment plant have potential to reduce the operational cost and improve the treatment performance, and scaling up MFCs will be essential. However, only a few studies have reported successful scale up attempts. Fabrication cost, treatment performance and operational lifetime are critical factors to optimize before commercialization of MFCs. To test these factors, we constructed a 20 L MFC system containing two 10 L MFC reactors and operated the system with brewery wastewater for nearly one year. Several operational conditions were tested, including different flowrates, applied external resistors, and poised anodic potentials. The condition resulting in the highest chemical oxygen demand (COD) removal efficiency (94.6 ± 1.0%) was a flow rate of 1 mL min-1 (HRT = 313 h) and an applied resistor of 10 Ω across each MFC circuit. Results from each of the eight stages of operation (325 days total) indicate that MFCs can sustain treatment rates over a long-term period and are robust enough to sustain performance even after system perturbations. possible ways to improve MFC performance were discussed for future studies.

Calcium alpha-ketoglutarate administration to malnourished hemodialysis patients improves plasma arginine concentrations.

Science.gov (United States)

Riedel, E; Hampl, H; Steudle, V; Nündel, M

1996-01-01

Calcium alpha-ketoglutarate administration to 24 malnourished hemodialysis patients for 1 year leads to a significant increase in plasma concentrations of L-arginine from 53.6 +/- 18.3 (compared to a healthy control group: 87.5 +/- 27.3) to 71.1 +/- 15.9 mumol/l (p calcium alpha-ketoglutarate administration.

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.

Long Term Financing of Infrastructure

OpenAIRE

Sinha, Sidharth

2014-01-01

Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...