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Sample records for long-term oral l-arginine

  1. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    PubMed

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  2. Protective effect of oral L-arginine administration on gentamicin-induced renal failure in rats.

    PubMed

    Can, C; Sen, S; Boztok, N; Tuglular, I

    2000-03-03

    We investigated the effects of orally supplemented L-arginine, the substrate of nitric oxide (NO) and N(omega)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide-synthase inhibitor in gentamicin-induced renal failure. Rats were given gentamicin (100 mg/kg/day s.c.), gentamicin and L-arginine (2 g/l, drinking water), gentamicin and L-NAME (100 mg/l, drinking water) or gentamicin plus L-arginine and L-NAME. After 8 days, the gentamicin group developed marked renal failure, characterized by a significantly decreased creatinine clearance and increased blood creatinine, fractional excretion of sodium, fractional excretion of lithium, urine gamma glutamyl transferase, systolic blood pressure and daily urine volume when compared to controls. Renal histological analysis confirmed tubular necrosis. L-arginine administration caused normalization of these parameters, whereas L-NAME led to aggravation of the failure. Concomitant administration of L-NAME and L-arginine to gentamicin-treated rats caused no significant changes when compared to the rats receiving gentamicin alone. We conclude that L-arginine supplementation has beneficial effects in gentamicin-induced renal failure in rats and that these effects are reversed by the NO-synthase inhibitor, L-NAME.

  3. Oral L-arginine improves endothelium-dependent dilation in hypercholesterolemic young adults.

    PubMed Central

    Clarkson, P; Adams, M R; Powe, A J; Donald, A E; McCredie, R; Robinson, J; McCarthy, S N; Keech, A; Celermajer, D S; Deanfield, J E

    1996-01-01

    In hypercholesterolemic rabbits, oral L-arginine (the substrate for endothelium derived nitric oxide) attenuates endothelial dysfunction and atheroma formation, but the effect in hypercholesterolemic humans is unknown. Using high resolution external ultrasound, we studied arterial physiology in 27 hypercholesterolemic subjects aged 29+/-5 (19-40) years, with known endothelial dysfunction and LDL-cholesterol levels of 238+/-43 mg/dl. Each subject was studied before and after 4 wk of L-arginine (7 grams x 3/day) or placebo powder, with 4 wk washout, in a randomized double-blind crossover study. Brachial artery diameter was measured at rest, during increased flow (causing endothelium-dependent dilation, EDD) and after sublingual glyceryl trinitrate (causing endothelium-independent dilation). After oral L-arginine, plasma L-arginine levels rose from 115+/-103 to 231+/-125 micromol/liter (P<0.001), and EDD improved from 1.7+/-1.3 to 5.6+/-3.0% (P<0.001). In contrast there was no significant change in response to glyceryl trinitrate. After placebo there were no changes in endothelium-dependent or independent vascular responses. Lipid levels were unchanged after L-arginine and placebo. Dietary supplementation with L-arginine significantly improves EDD in hypercholesterolemic young adults, and this may impact favorably on the atherogenic process. PMID:8621785

  4. Myocardial fibrosis is unaltered by long-term administration of L-arginine in dystrophin deficient mdx mice: a histomorphometric analysis.

    PubMed

    Marques, Maria Julia; Barbin, Isabel Cristina Chagas; Taniguti, Ana Paula Tiemi; Oggian, Daniela Silva; Ferretti, R; Santo Neto, H

    2010-06-01

    Cardiac failure secondary to myocardial fibrosis (MF) significantly contributes to death in Duchenne muscular dystrophy (DMD), a fatal form of muscle disease. In aging, the mdx mice, an animal model of DMD, MF is similar to that observed in humans. Nitric oxide-based therapy has been proposed to retard MF in DMD and a candidate is L-arginine (L-arg). In this study we evaluated the effects of long-term therapy with L-arg in the MF of mdx mice. mdx mice (6 months old) were treated with L-arg in drinking water. Control mdx mice received water only. After 15 months of treatment, hearts were stained with Masson's trichrome for analysis of MF and with hematoxilyn and eosin for analysis of inflammation and cardiomyocyte damage. We observed that MF was not affected (29.5 +/- 2.5% of MF area for control vs 31.4 +/- 2% for L-arginine-treated animals; P > 0.05). The density of inflammatory cells was reduced (169 +/- 12 cells/mm 2 in control vs 102 +/- 9 cells/mm 2 in L-arg-treated; P < 0.05). The present study shows that long-term administration of L-arg is not effective in retarding MF in mdx dystrophinopathy.

  5. L-arginine destabilizes oral multi-species biofilm communities developed in human saliva.

    PubMed

    Kolderman, Ethan; Bettampadi, Deepti; Samarian, Derek; Dowd, Scot E; Foxman, Betsy; Jakubovics, Nicholas S; Rickard, Alexander H

    2015-01-01

    The amino acid L-arginine inhibits bacterial coaggregation, is involved in cell-cell signaling, and alters bacterial metabolism in a broad range of species present in the human oral cavity. Given the range of effects of L-arginine on bacteria, we hypothesized that L-arginine might alter multi-species oral biofilm development and cause developed multi-species biofilms to disassemble. Because of these potential biofilm-destabilizing effects, we also hypothesized that L-arginine might enhance the efficacy of antimicrobials that normally cannot rapidly penetrate biofilms. A static microplate biofilm system and a controlled-flow microfluidic system were used to develop multi-species oral biofilms derived from pooled unfiltered cell-containing saliva (CCS) in pooled filter-sterilized cell-free saliva (CFS) at 37° C. The addition of pH neutral L-arginine monohydrochloride (LAHCl) to CFS was found to exert negligible antimicrobial effects but significantly altered biofilm architecture in a concentration-dependent manner. Under controlled flow, the biovolume of biofilms (μm(3)/μm(2)) developed in saliva containing 100-500 mM LAHCl were up to two orders of magnitude less than when developed without LAHCI. Culture-independent community analysis demonstrated that 500 mM LAHCl substantially altered biofilm species composition: the proportion of Streptococcus and Veillonella species increased and the proportion of Gram-negative bacteria such as Neisseria and Aggregatibacter species was reduced. Adding LAHCl to pre-formed biofilms also reduced biovolume, presumably by altering cell-cell interactions and causing cell detachment. Furthermore, supplementing 0.01% cetylpyridinium chloride (CPC), an antimicrobial commonly used for the treatment of dental plaque, with 500 mM LAHCl resulted in greater penetration of CPC into the biofilms and significantly greater killing compared to a non-supplemented 0.01% CPC solution. Collectively, this work demonstrates that LAHCl moderates multi

  6. l-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

    PubMed Central

    He, Jinzhi; Hwang, Geelsu; Liu, Yuan; Gao, Lizeng; Kilpatrick-Liverman, LaTonya; Santarpia, Peter; Zhou, Xuedong

    2016-01-01

    ABSTRACT l-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous l-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, l-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous l-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) l-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical l-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, l-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H2O2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H2O2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of l-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. IMPORTANCE

  7. Urinary nitrate excretion in relation to murine macrophage activation. Influence of dietary L-arginine and oral NG-monomethyl-L-arginine.

    PubMed

    Granger, D L; Hibbs, J B; Broadnax, L M

    1991-02-15

    Murine macrophage oxidation of L-arginine guanidino nitrogen to nitrite/nitrate yields an intermediate effector, possibly nitric oxide, with antimicrobial activity. Total body nitrogen oxidation metabolism (NOM) was measured in vivo by determining the urinary nitrate excretion of mice ingesting a chemically defined nitrite/nitrate-free diet. As reported previously, mycobacterial infection with bacillus Calmétte-Guerin led to a large increase in urinary nitrate excretion. This increase was temporally related to macrophage activation in vivo. The substrate for macrophage nitrogen oxidation metabolism in vitro, L-arginine, was deleted from the diet without ameliorating the urinary nitrate excretion response induced by BCG. This suggested that L-arginine was synthesized endogenously because there are no other known natural substrates for NOM. A competitive inhibitor of NOM, the L-arginine analog, NG-monomethyl-L-arginine was fed to mice in their drinking water. NG-monomethyl-L-arginine ingestion blocked both basal and bacillus Calmétte-Guerin-induced urinary nitrate excretion over a 2-4 week time span. These experimental conditions should prove useful for further investigation on the role of macrophage NOM in host defense against intracellular microorganisms.

  8. Oral administration of both tetrahydrobiopterin and L-arginine prevents endothelial dysfunction in rats with chronic renal failure.

    PubMed

    Yamamizu, Kohei; Shinozaki, Kazuya; Ayajiki, Kazuhide; Gemba, Munekazu; Okamura, Tomio

    2007-03-01

    We examined the mechanism of endothelial dysfunction in chronic renal failure (CRF), with reference to NO synthase. CRF was induced by 5/6 nephrectomy in rats. Either L-arginine (1.25 g/L in drinking water), tetrahydrobiopterin (BH4, 10 mg/kg per day in food), or a combination of the 2 were orally administered to CRF rats for 9 weeks. CRF rats showed elevation of systolic blood pressure compared with sham-operated rats. Endothelium-dependent relaxation induced by acetylcholine or A23187 in the isolated aorta was significantly reduced, and in vitro treatment with L-arginine, BH4, or superoxide dismutase restored the relaxation. Aortic segments from CRF rats showed significantly higher superoxide production in response to A23187, which was inhibited by L-NAME. Plasma concentrations of asymmetric dimethylarginine and symmetric dimethylarginine were higher in CRF rats. These changes in CRF rats were totally or partially decreased by L-arginine or BH4 supplementation in vivo. Interestingly, the combined treatment showed additive effects in certain parameters. These results suggest that vascular disorders in CRF rats may be partly due to NOS uncoupling caused by a relative deficiency of BH4 and partially due to accumulation of endogenous inhibitors of NOS and L-arginine uptake, resulting in the decrease of NO production and the increase of reactive oxygen species.

  9. Diabetic nephropathy is resistant to oral l-arginine or l-citrulline supplementation

    PubMed Central

    You, Hanning; Gao, Ting; Cooper, Timothy K.; Morris, Sidney M.

    2014-01-01

    Our recent publication showed that pharmacological blockade of arginases confers kidney protection in diabetic nephropathy via a nitric oxide (NO) synthase (NOS)3-dependent mechanism. Arginase competes with endothelial NOS (eNOS) for the common substrate l-arginine. Lack of l-arginine results in reduced NO production and eNOS uncoupling, which lead to endothelial dysfunction. Therefore, we hypothesized that l-arginine or l-citrulline supplementation would ameliorate diabetic nephropathy. DBA mice injected with multiple low doses of vehicle or streptozotocin (50 mg/kg ip for 5 days) were provided drinking water with or without l-arginine (1.5%, 6.05 g·kg−1·day−1) or l-citrulline (1.66%, 5.73 g·kg−1·day−1) for 9 wk. Nonsupplemented diabetic mice showed significant increases in albuminuria, blood urea nitrogen, glomerular histopathological changes, kidney macrophage recruitment, kidney TNF-α and fibronectin mRNA expression, kidney arginase activity, kidney arginase-2 protein expression, and urinary oxidative stress along with a significant reduction of nephrin and eNOS protein expression and kidney nitrite + nitrate compared with normal mice after 9 wk of diabetes. Surprisingly, l-arginine or l-citrulline supplementation in diabetic mice did not affect any of these parameters despite greatly increasing kidney and plasma arginine levels. These findings demonstrate that chronic l-arginine or l-citrulline supplementation does not prevent or reduce renal injury in a model of type 1 diabetes. PMID:25320354

  10. Long-term effects of early life L-arginine supplementation on growth performance, lymphoid organs and immune responses in Leghorn-type chickens.

    PubMed

    Deng, K; Wong, C W; Nolan, J V

    2005-06-01

    The effects of a short-term dietary arginine supplementation after hatching on subsequent growth and the immune system were assessed in growing male Leghorn-type chickens. An arginine-deficient basal diet (67 g/kg) supplemented with 0 (control), 2.7 (LA) or 5.4 (HA) g L-arginine/kg, was offered ad libitum to 1-d-old male ISA Brown chicks for 4 weeks, then all birds were offered ad libitum a commercial pullet grower feed (8.9 g arginine/kg) for another 8 weeks. Supplemented birds had higher growth rates and feed intake than control birds during the 4-week supplementation period, but these effects did not persist into the subsequent periods. When the supplementation ceased at week 4, no differences in lymphoid organ weights relative to body weight (BW), primary serum antibody levels against sheep red blood cells (SRBC) or cutaneous reactivity of toe webs to phytohaemagglutinin (PHA) were detected. LA-fed birds had lower immunoglobulin (Ig) G levels against bovine serum albumin (BSA) than the control at week 4, but this effect did not persist at weeks 8 and 12. No difference in anti-BSA IgM levels was detected among birds at week 4; at week 12, however, the LA-fed birds had a significantly higher anti-BSA IgM level than the control. An increased anti-SRBC antibody level and a reduced relative bursa weight in HA-fed birds were evident at week 8, without any prior effects. It is concluded that short-term supplementary L-arginine had minimal effects on immunity, but some enhancement of SRBC antibody responses in later stages of growth was observed with previous L-arginine administration.

  11. Long-term oral antiarrhythmic therapy with mexiletine.

    PubMed Central

    Campbell, N P; Pantridge, J F; Adgey, A A

    1978-01-01

    Forty-eight patients with ischaemic heart disease received oral mexiletine for the control or prevention of ventricular arrhythmias. The most frequently used doses were 200, 250, and 300 mg 8-hourly. The treatment period varied from 2 days to more than 1 year (median 3 months). No ventricular arrhythmias were detected in more than one-half of the patients. Severe side effects occurred in 15 (31%) of the 48 patients. Major ventricular arrhythmias were observed in 14 (29%) of the 48 patients at a time when the majority had plasma concentrations within the therapeutic range. The value of mexiletine in the management of patients at risk of sudden death is likely to be limited. PMID:687477

  12. Target outcomes for long-term oral health care in dementia: a Delphi approach.

    PubMed

    Jones, J A; Brown, E J; Volicer, L

    2000-01-01

    This study developed a list of target outcomes for long-term oral health care in persons with dementia. A three-round Delphi study was used to develop a list of target outcomes. Participants included 99 staff and 171 family members associated with the Dementia Special Care Unit in Bedford, MA. In Round 1 participants were asked to list five outcomes for long-term oral health care. Items were grouped, redundancies removed, and fed back in Round 2, when participants scored the items from 1 (least important) to 10 (most important). Round 2 responses were tabulated and the top 20 were fed back for scoring in Round 3. The top 10 target outcomes in decreasing order of importance were: patient will be free from oral pain, patient will not be at risk for aspiration, emergency dental treatment will be available when needed, prevent mouth infections, daily mouth care is as much a part of daily care as shaving or brushing hair, prevent discomfort from loose teeth or sore gums, teeth will be brushed thoroughly once a day, staff will be able to provide oral hygiene care as needed, provide dental care to prevent problems eating, and recognize oral problems early. Family and professional caregivers were remarkably consistent in their identification of the top 10 outcomes. Further work is needed to ensure broad international and interdisciplinary acceptance (including families and the long-term care residents themselves) of target outcomes for long-term oral health care in persons with dementia.

  13. Prevention of oral disease for long-term care and homebound elderly.

    PubMed

    Lambert, Nicole Madison; Tepper, Lynn M

    2010-01-01

    Despite the fact that many oral diseases afflicting the long-term care or homebound elderly are preventable or treatable, many older people do not seek available treatment, or their oral health care needs are not being met. The dental profession must, therefore, increase the preventative dental awareness of elders and make preventative and treatment services more accessible to this population. Interdisciplinary training and collaborative efforts among the dental profession, medical profession and caregivers are necessary in preventing oral disease for this geriatric population, which would improve not just oral health, but overall systemic health as well, thereby improving their quality of life.

  14. Cardioprotective activity of placental growth factor combined with oral supplementation of l-arginine in a rat model of acute myocardial infarction

    PubMed Central

    Luo, Liyun; Chen, Bairong; Huang, Yin; Liang, Zibin; Li, Songbiao; Yin, Yuelan; Chen, Jian; Wu, Wei

    2016-01-01

    Objective Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI. Materials and methods Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson’s staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed. Results Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group (P<0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group (P<0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group (P<0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group (P<0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group (P<0.01). Conclusion Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l-arginine

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

    PubMed Central

    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. PMID:26309137

  16. Long-term drug administration in the adult zebrafish using oral gavage for cancer preclinical studies

    PubMed Central

    Dang, Michelle; Henderson, Rachel E.; Garraway, Levi A.

    2016-01-01

    ABSTRACT Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAFV600E inhibitor, Vemurafenib, in adult zebrafish harboring BRAFV600E melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases. PMID:27482819

  17. ACTIVITY AND ISOZYME CONTENT OF LACTATE DEHYDROGENASE UNDER LONG-TERM ORAL TAURINE ADMINISTRATION TO RATS.

    PubMed

    Ostapiv, R D; Humenyuk, S L; Manko, V V

    2015-01-01

    The effect of long-term oral taurine administration to rats on activity of lactate dehydrogenase (LDH), its isozyme content and activity in the whole blood, liver, thigh muscle, brain and testes tissues were studied in the present work. For this purpose male Wistar rats with body weight 190-220 g were randomly divided into three groups, they were orally administered drinking water (control group) or taurine solution 40 and 100 mg per kg of body weight ( groups I and II, respectively). The total lactate dehydrogenase activity was measured spectrophotometrically, the percentage content of isozymes was determined by electrophoresis in 7.5% poliacrylamide gel withfurther staining according to J. Garbus. It was found that the total lactate dehydrogenase activity increased in all studied tissues. In testes of animals of both groups and in brain of group I animals, the total percentage contents of isozymes that are responsible for lactate production (LDH4+LDH5) increased. In liver of animals of both groups and in whole blood of group II animals, the total percentage content of isozymes that produce pyruvate (LDH1+LDH2) increased. In thigh muscle of both groups and in brain of group II animals the balance between LDH1+LDH2 and LDH4+LDH5 content did not differ from control values, though total lactate dehydrogenase activity was significantly higher, than that in the control group. Thus, the increase in the lactate dehydrogenase activity under long-term oral taurine administration in different rat tissues was found to be tissue- and dose-dependent and was caused by the increase in the content of different isozymes. Such increase in group I animals might be explained by adaptive mechanisms to hypoxia caused by high doses of taurine. For group II animals high doses of taurine were toxic and directly affected metabolic processes in the animal bodies.

  18. Reducing the risk of aspiration pneumonia among elderly patients in long-term care facilities through oral health interventions.

    PubMed

    Sarin, Jaya; Balasubramaniam, Ramesh; Corcoran, Amy M; Laudenbach, Joel M; Stoopler, Eric T

    2008-02-01

    Aspiration pneumonia is a leading cause of morbidity and mortality of elderly residents in long-term care facilities. The microflora present in the oral cavity because of poor oral hygiene has been associated with aspiration pneumonia. There is evidence that improved oral care can reduce the risk of developing aspiration pneumonia in the elderly. The purpose of this paper is to review aspiration pneumonia and provide oral health care guidelines in an effort to help reduce the risk of aspiration pneumonia in the elderly residing in long-term care facilities.

  19. Short- and long-term effects of oral vancomycin on the human intestinal microbiota

    PubMed Central

    Isaac, Sandrine; Scher, Jose U.; Djukovic, Ana; Jiménez, Nuria; Littman, Dan R.; Abramson, Steven B.; Pamer, Eric G.; Ubeda, Carles

    2017-01-01

    Background Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. Methods We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. Results During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. Conclusions Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost–benefit equation for antibiotic prescription. PMID

  20. Oral status and treatment needs among elderly within municipal long-term care 2002-2004.

    PubMed

    Isaksson, Rita; Söderfeldt, Björn

    2007-01-01

    A supplementary regulation in the Swedish National Dental Health Care Insurance stipulates an increased economic support to those, who are dependent permanently due to disease or handicap. Once enlisted to care, they are entitled to an annual dental examination and individual prophylactic advice free of charge, and to necessary dental treatment, offered within the ordinary medical care, regulated and funded by the county council. A population of persons, > or = 65 years of age and enrolled in municipal long-term care (LTC) in a county in the south of Sweden, was followed regarding changes in oral status and treatment needs for two years. The number of persons examined the year 2002 was 2416 and the corresponding figure for 2004 was 2846. Totally 1170, i.e. 48.4%, of those examined 2002 were deceased two years after the initial examination. Only 914, assessed in 2002, were available for assessment with full data at follow up 2004 and the results are based upon assessments in this group. Analyzing the assessed variables (dental status, oral hygiene status, oral mucosal inflammation, oral mucosal friction) revealed a change during these two years. Significant impairments were recognised, regarding mucosal inflammation and mucosal friction. Regarding treatment needs assessed by a dentist and a dental hygienist, there was a maintained and even increased need for extensive treatment, both by the dentist and, to a greater extent, by the dental hygienist. In sum, prevention efforts both from the dental profession and from other care providers are important to achieve and maintain acceptable oral status.

  1. Long-term oral sodium bicarbonate supplementation does not improve serum albumin levels in hemodialysis patients.

    PubMed

    Bossola, Maurizio; Giungi, Stefania; Tazza, Luigi; Luciani, Giovanna

    2007-01-01

    Metabolic acidosis, a frequent event in hemodialysis patients, has been implicated as a potential cause of protein-energy malnutrition. Unfortunately, correction of metabolic acidosis by means of high bicarbonate concentration in the dialysate does not seem to lead to significant changes in nutritional parameters. The project was a single-arm, open-label, 12-month pilot study at a university-based tertiary care center aimed at evaluating whether correction of metabolic acidosis through long-term oral sodium bicarbonate supplementation improves serum albumin levels and other nutritional parameters in patients undergoing maintenance hemodialysis. Twenty highly acidotic hemodialysis patients patients were invited to consume an oral supplementation of sodium bicarbonate (1 g, thrice daily), for 12 months. Patients were followed at baseline and every month, until month 12. At each follow-up visit, dry body weight, BMI, blood pressure, presence of edema, venous bicarbonate, and serum albumin were measured. Total lymphocyte count, fasting total cholesterol and C-reactive protein were assessed every 2 months. At baseline and at 12 months, the subjective global assessment of nutritional status and the protein equivalent of nitrogen appearance normalized to actual body weight were determined. Plasma bicarbonate level rose from 18.1 +/- 2.7 to 22.1 +/- 4.5 mmol/l after 10 months (p = 0.001). Mean serum albumin levels were 3.8 +/- 0.2 mg/dl at baseline and 3.9 +/- 0.2 at the end of the study. Repeated measure ANOVA showed that there was no significant effect of bicarbonate treatment on serum albumin levels (p = 0.29), dry weight (p = 0.1), serum total cholesterol (p = 0.97), total lymphocyte count (p = 0.69), or C-reactive protein (p = 0.85). Mean subjective global assessment score was 4.53 +/- 0.37 at baseline and 4.58 +/- 0.54 at 12 months (p = 0.1). Mean nPNA (g/kg/day) was 0.86 +/- 0.05 at baseline and 0.85 +/- 0.08 at month 12. The present study demonstrates that long-term

  2. Long-term efficacy of oral encainide in frequent and repetitive ventricular arrhythmias.

    PubMed

    Bongiorni, M G; Levorato, D; Arlotta, C; Paperini, L; Contini, C

    1988-07-01

    The short- and long-term efficacy of oral encainide was studied in 14 patients with chronic high-frequency ventricular arrhythmias and in 14 patients with chronic frequent episodes of non-sustained ventricular tachycardia (NSVT). Encainide efficacy was assessed during a dose-titration period and in a 36-month follow-up also studying the drug effects on routine haematologic data and left ventricular function (LVF). During dose-titration, encainide caused a 78.3% decrease in the average hourly frequency of isolated PVC and a 96.1% reduction in NSVT episodes in the two groups of patients. On follow-up (11 patients in each group) the mean percentage reductions were 95.1% in isolated PVC and 99.7% in NSVT episodes. Encainide did not impair LVF as showed by the comparison of echocardiographic fractional shortening before and after 12 months of treatment. Minor adverse effects of encainide were dose-related visual disturbances in two patients. A major adverse effect was the appearance of sustained VT in one NYHA class IV patient. Oral encainide effectively reduces the frequency of PVC and NSVT, it does not impair left ventricular function and it is associated with infrequent minor side effects. Uncommon, but severe, side effects may appear in patients with marked impairment of left ventricular function.

  3. Evaluation of the long-term oral consequences of equine exodontia in 50 horses.

    PubMed

    Townsend, Neil B; Dixon, Padraic M; Barakzai, Safia Z

    2008-12-01

    The aims of this study were to objectively evaluate and quantify the process of post-extraction cheek teeth (CT) dental drift in horses, and to report on associated disorders of CT wear and long-term periodontal health. Fifty horses that had CT oral extraction because of apical infection were prospectively re-examined and a full oral examination, including measurements of some dental parameters, was performed. Narrowing of the extraction space was noted in all cases with complete closure occurring in 18% of horses. The rate of dental drift was calculated as 15.7% of extraction space/year (range 4-50%) and was not associated with the age at extraction (P=0.78) or frequency of dental care since extraction (P=0.48). There was a significant negative relationship between the rate of dental drift and the duration of time since extraction (P=0.008). Overgrowths were present on the opposite CT row in 98% of horses, including opposite the extracted CT and on the Triadan 06s and 11s. No significant difference was noted in either the number of diastemata (P=0.9) or periodontal disease score (P=0.8) between the extraction and the contralateral cheek tooth rows.

  4. Long-Term Immunological Memory Induced by Recombinant Oral Salmonella Vaccine Vectors

    PubMed Central

    Kohler, James J.; Pathangey, Latha; Hasona, Adnan; Progulske-Fox, Ann; Brown, Thomas A.

    2000-01-01

    We have previously shown that Salmonella enterica serovar Typhimurium expressing the hagB hemagglutinin gene from Porphyromonas gingivalis can induce primary and recall immune responses in serum and secretions in mice; however, the longevity of memory induced by oral Salmonella carriers has not been adequately demonstrated. In this study, we examined the capacity of mice to mount a recall response 52 weeks after primary immunization. Recall responses were seen in serum immunoglobulin G (IgG) and IgA following boosting at week 52, and in most cases, they were equal to or greater than the primary responses. Significant mucosal IgA recall responses in saliva and vaginal wash were also detected following boosting at week 52. In addition, there was a considerable residual response in secretions at week 51, prior to boosting. These results indicate that oral Salmonella vectors can induce long-term memory to recombinant HagB and are particularly effective at inducing long-lasting mucosal responses as well as at inducing the capacity for mucosal recall responses. PMID:10858264

  5. Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients.

    PubMed

    Krüger, Thilo; Brandenburg, Vincent; Schlieper, Georg; Marx, Nikolaus; Floege, Jürgen

    2013-03-01

    End-stage renal disease (ESRD) patients exhibit an increased risk of bleeding compared with non-chronic kidney disease (CKD) patients due to uraemic platelet dysfunction, altered vessel architecture and other factors. This renders any long-term oral anticoagulation potentially difficult. While there is little doubt that ESRD patients with recurrent thromboembolism or a mechanical cardiac valve should receive vitamin K antagonists (coumarins), the use of coumarins in ESRD patients with atrial fibrillation is a matter of debate. In non-CKD patients, current guidelines strongly recommend the use of oral anticoagulants for stroke prophylaxis in atrial fibrillation if certain risk factors are present (CHA2DS2-VASc score). This recommendation is often extrapolated to patients with advanced CKD or ESRD but data supporting this practice are weak to absent. Besides an increased bleeding risk in ESRD patients, coumarins will also accelerate cardiovascular calcification and are potent risk factors for the development of calcific uraemic arteriolopathy (calciphylaxis). Novel coumarin alternatives such as direct thrombin inhibitors are promising but none is currently approved for use in ESRD patients. Whether interventional treatment strategies such as atrial appendage occlusion are safe and effective options in advanced CKD is also as yet unresolved. This review attempts to balance the potential risks and benefits of coumarin usage in ESRD patients and to give the best possible recommendations for everyday patient care.

  6. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    PubMed

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  7. Long-term efficacy of oral calcium polystyrene sulfonate for hyperkalemia in CKD patients

    PubMed Central

    Yu, Mi-Yeon; Yeo, Jee Hyun; Park, Joon-Sung; Lee, Chang Hwa

    2017-01-01

    Background Calcium polystyrene sulfonate (CPS) has long been used to treat hyperkalemia in patients with chronic kidney disease (CKD). However, its efficacy and safety profile have not been systematically explored. We investigated the long-term efficacy of oral CPS for treating mild hyperkalemia on an outpatient basis. Methods We performed a retrospective analysis of ambulatory CKD patients who were prescribed CPS for > 1 week because of elevated serum potassium levels > 5.0 mmol/L. Patients were divided into four groups according to the length of time that they took a fixed dosage of CPS (Group 1, < 3 months; Group 2, 3–6 months; Group 3, 6–12 months; and Group 4, > 1 year). Response was defined as a decrease in the serum potassium level (> 0.3 mmol/L) after treatment with CPS. Results We enrolled a total of 247 adult patients with a basal eGFR level of 30 ± 15 mL/min/1.73 m2. All patients took small doses of CPS (8.0 ± 3.6 g/d), and serum potassium decreased in a dose-dependent fashion. Serum potassium of all patients decreased significantly from 5.8 ± 0.3 mmol/L to 4.9 ± 0.7 mmol/L with CPS treatment (P < 0.001). The response rates were 79.9%, 71.4%, 66.7%, and 86.8% in Groups 1, 2, 3, and 4, respectively. No serious adverse effects were reported during CPS administration, though constipation was noted in 19 patients (8%). Conclusion Small doses of oral CPS are effective and safe for controlling mild hyperkalemia in CKD patients over a long period of time. PMID:28328954

  8. Effects of long-term use of HAART on oral health status of HIV-infected subjects

    PubMed Central

    Nittayananta, Wipawee; Talungchit, Sineepat; Jaruratanasirikul, Sutep; Silpapojakul, Kachornsakdi; Chayakul, Panthip; Nilmanat, Ampaipith; Pruphetkaew, Nannapat

    2011-01-01

    BACKGROUND The aim of this study was to determine the effects of long-term use of highly active antiretroviral therapy (HAART) on oral health status of HIV-infected subjects. METHODS Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in HIV-infected subjects with and without HAART, and in non-HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long-term use of HAART on oral health status of HIV-infected subjects. RESULTS: One hundred and fifty-seven HIV-infected subjects – 99 on HAART (age range 23–57 years, mean 39 years) and 58 not on HAART (age range 20–59 years, mean 34 years) – and 50 non-HIV controls (age range 19–59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV-infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short-term HAART (P < 0.01). The subjects with long-term HAART were found to have a greater risk of having oral lesions than those with short-term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). CONCLUSION We conclude that long-term HAART has adverse effects on oral health status of HIV-infected subjects. PMID:20202089

  9. An oral yohimbine/l-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects

    PubMed Central

    Kernohan, A F B; McIntyre, M; Hughes, D M; Tam, S W; Worcel, M; Reid, J L

    2005-01-01

    Aims Interaction of phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction with organic nitrates could lead to severe hypotension. NMI 861 is a combination of 7.7 mg yohimbine tartrate and 6 g l-arginine glutamate. A similar oral combination, which contains the same amount of yohimbine and l-arginine, has been shown to improve erectile function in previous studies. Methods In two placebo-controlled, randomized, double-blind, two-way crossover design studies we aimed to assess first the pharmacokinetics and pharmacodynamics of a single oral dose of NMI 861 administered in 16 healthy male subjects, and then the pharmacodynamics of orally administered NMI 861 in combination with intravenous nitroglycerine (GTN) in 12 healthy male subjects. Systolic (SBP) and diastolic (DBP) blood pressures, pulse rate and adverse events were measured in each study. Results NMI 861 was well tolerated by all subjects with no significant adverse reactions reported. For l-arginine, mean Cmax ± SEM (range) was 42 ± 2.2 (28–63) µg ml−1 and tmax (range) was 0.88 (0.50–1.5) h. AUC and t1/2 were not calculated for l-arginine because of the presence of endogenous concentrations and the contribution from food sources. For yohimbine, mean Cmax was 42 ± 11 (2.8–128) ng ml−1; tmax was 0.57 (0.25–1.0) h; mean AUC(0,8 h) was 65 ± 24 (5.4–332), ng ml−1 h and t1/2 was 1.0 ± 0.34 (0.40–6.0) h. There was a small but significant difference in the mean change from baseline for SBP from 0 to 6 h after NMI 861 treatment compared with placebo (0.8 ± 1.4 vs−4.1 ± 2.1 mmHg, respectively; 95% Cl 0.0, 9.8 mmHg (P = 0.047)). There was no significant difference in SBP between treatments for the studied periods 6–12 h and 12–24 h. There was no significant difference in DBP or pulse between NMI 861 and placebo treatments for the three studied time periods. In the study designed to investigate the interaction of organic nitrate with NMI 861, subjects were infused

  10. L-arginine independent macrophage tumor cytotoxicity

    SciTech Connect

    Klostergaard, J.; Leroux, M.E. )

    1989-12-29

    We have investigated the role of L-arginine in macrophage tumor cytotoxicity in coculture. L929, EMT-6, MCA-26, and P815 targets were all susceptible to cytolysis by activated macrophages when cocultured in medium containing L-arginine. When cocultured in arginine-free medium, these targets displayed comparable or even higher levels of lysis. L1210 targets were lytically resistant under either condition. However, 59Fe release from this target did reflect strong dependence on the presence of arginine. The structural analogue, NG-monomethyl-L-arginine, was an effective inhibitor of iron-release from L1210 targets cocultured with activated macrophages, whereas it had minimal inhibitory effects on release of 51Cr from cocultured L929 cells. These results suggest that the L-arginine requiring cytotoxic pathway of activated macrophage is independent of major effector mechanisms involved in tumor cell lysis.

  11. Comparison of Dental Caries Experience in Children Suffering From Epilepsy with and without Administration of Long Term Liquid Oral Medication

    PubMed Central

    Bhadravathi, Manjunath Chaluvaiah; Kumar, Adarsh; Narang, Ridhi; Gupta, Ambika; Singh, Harneet

    2016-01-01

    Introduction Sucrose is added as sweetening agent in liquid oral medication (LOM) to mask the acrid taste of medicines which may be potentially cariogenic. Many children under long term LOM therapy for treatment of epilepsy may be susceptible to dental caries. Aim To assess and compare dental caries experience in children under long term liquid oral medication with those not under such medication among 2-12 years old children suffering from epilepsy. Materials and Methods A cross-sectional study was undertaken on a total of 84 children aged 2–12 years, who were suffering from epilepsy receiving liquid oral medication for more than 3 months were selected (study group) and for comparison 106 children of similar age group and disease but on other forms of medication were included as control group. Dental caries was assessed using DMFT/DMFS (Decayed, Missing, Fillled Teeth / Surfaces), dmft/dft and dmfs/dfs indices. One-way ANOVA and t-test were used with p-value fixed at 0.05. Univariate logistic regression was applied. Results Children on LOM were at increased risk of dental caries than those with other forms of medications (OR: 2.55, 95% CI (2.37-4.15) p=0.000, HS). Caries prevalence was high in the study group (76.1%) when compared to control group (55.6%). Conclusion Long term use of liquid medicines containing sucrose is a risk factor for dental caries among children with epilepsy. PMID:27504416

  12. An early oral health care program starting during pregnancy: results of a prospective clinical long-term study.

    PubMed

    Meyer, Karen; Geurtsen, Werner; Günay, Hüsamettin

    2010-06-01

    This study covers phase IV of a prospective clinical long-term study. Objective of this clinical investigation was to analyze the effects of a long-term prevention program on dental and oral health of teenagers at the age of 13 to 14 years. The entire study was subdivided into four phases. Phase I comprised an individual preventive care during pregnancy ("primary-primary prevention"); phase II assessed mothers and their young children until the age of 3 years ("primary prevention"); and in phase III, mothers and children at the age of 6 years were investigated. In phase IV of the study, the oral health of 13- to 14-year-old teenagers was examined (13.4 +/- 0.5 years; n = 29). All phases consisted of an examination, education about oral health care, and treatment based on the concept of an early oral health care promotion. The control group consisted of randomly selected adolescents at the same age (n = 30). The following clinical parameters were assessed: decayed/missing/filled teeth (DMF-T)/decayed, missing, and filled surface teeth index, hygiene index, papilla bleeding index, Periodontal Screening Index, and Streptococcus mutans/Lactobacillus concentration in saliva. The teenagers of the "prevention" group of phase IV of our prospective study revealed a share of 89.7% caries-free dentitions (65.5% sound; 24.2% caries-free with fillings). Mean DMF-T was 0.55 +/- 1.0. The control group showed a significantly higher mean DMF-T of 1.5 +/- 1.5 (p < 0.05) and revealed 56.7% of caries-free dentitions (30% sound, 26.7% caries-free with restorations). Our data clearly document that an early oral health care promotion starting during pregnancy may cause a sustained and long-term improvement of the oral health of children.

  13. Improving the oral health of older people in long-term residential care: a review of the literature.

    PubMed

    Miegel, Karen; Wachtel, Tracey

    2009-06-01

    Background.  Unrefutable evidence now links poor oral health with the development of preventable systemic illnesses and debilitating conditions that threaten quality of life and life itself. This is especially significant for an increasing older population who are dependent on others for care. Aims and objectives.  The majority of studies analysing the oral health of older dependent people in long-term residential care have been undertaken by dental professionals. This critical literature review examines the issue from a nursing perspective because nursing care providers have a fundamental role in daily oral health provision for dependent residents. Conclusions.  Multiple barriers were found to negatively impact on daily oral healthcare provision, including lack of care provider education, oral health values, availability of resources, implementation of supportive policies, documentation and oral health assessment tools. Relevance to clinical practice.  The nursing profession, at all levels, must become pro-active in removing financial, political and workforce barriers that impact negatively on oral health outcomes. A multi-faceted approach is required to address these barriers, including development and implementation of oral health education programmes, assessment screening tools, care plans, documentation, supply of oral hygiene aids and the appointment of oral care 'champions'.

  14. Oral Finasteride Presents With Sexual-Unrelated Withdrawal in Long-Term Treated Androgenic Alopecia in Men.

    PubMed

    Perez-Mora, Nicolas; Velasco, Carlos; Bermüdez, Fernando

    2015-01-01

    Side effects associated with oral finasteride (FT) (1 mg/d) and topical 5% minoxidil (M5) have been previously described. The authors have evaluated long-term adverse effects and causes of long-term therapy withdrawal in patients with androgenic alopecia (AGA) treated with M5+FT vs M5 without FT. A total of 130 AGA patients with a minimum 2-year follow-up volunteered to complete a questionnaire on side effects. Patients' responses were classified as "never," "rarely," "sometimes," "often," and "all the time." An adverse effect was considered in the presence of an "often" or "all the time" response. A total of 100 patients received combined M5+FT and were compared with 30 patients receiving single-therapy M5 according to the physician's clinical criteria. Erectile dysfunction (3%), diminished libido (4%), and reduced ejaculation (7%) were present in patients taking M5+FT but were absent in patients taking M5. Only 1 of 100 patients taking M5+FT quit long-term therapy due to sexual adverse effects (diminished libido). The main causes for therapy withdrawal in the FT group were lack of positive results in 11% and in the M5 group side effects in 4% (P < .02). Increased body hair was different between groups: with 6.6% in the M5 group and 4% in the M5+FT group (P < .03). FT demonstrates sexual-unrelated reasons as the main cause of therapy withdrawal in long-term treated AGA patients.

  15. Long-term safety and efficacy of oral phentolamine mesylate (Vasomax) in men with mild to moderate erectile dysfunction.

    PubMed

    Padma-Nathan, H; Goldstein, I; Klimberg, I; Coogan, C; Auerbach, S; Lammers, P

    2002-08-01

    The objectives of this study were to evaluate long-term safety and efficacy of phentolamine mesylate, an orally active, rapid-acting alpha-adrenergic receptor antagonist, for the treatment of men suffering from erectile dysfunction (ED). It was an open-label study involving more than 2000 patients. Men received phentolamine mesylate 40 mg or 80 mg (10 tablets/month) as needed for up to 13 months and self-assessed erectile performance using two validated questionnaires. Treatment with phentolamine mesylate was associated with increases in Erectile Function Domain score of the IIEF, successful vaginal penetrations, and in overall satisfaction. Most adverse events were mild or moderate in severity and consistent with the known pharmacodynamic properties of phentolamine. In conclusion, phentolamine mesylate is safe and effective in the long-term treatment of men with mild to moderate ED.

  16. [L-arginine and male infertility].

    PubMed

    Scibona, M; Meschini, P; Capparelli, S; Pecori, C; Rossi, P; Menchini Fabris, G F

    1994-12-01

    The clinical efficacy and acceptance of L-arginina HCL was tested in 40 infertile men. All of these men had a normal number of spermatozoa (> 20 million/ml), but a decreased motility; this decreased motility was not due to infection or to immunological disorders. The treatment consisted of 80 ml of 10% L-arginine HCL administered daily per os for 6 months. L-arginine HCL showed to be able to improve the motility of spermatozoa without any side-effects.

  17. Effectiveness of Long Term Supervised and Assisted Physiotherapy in Postsurgery Oral Submucous Fibrosis Patients

    PubMed Central

    Srivastava, N.; Bagga, V.; Shetty, A.

    2016-01-01

    Oral submucous fibrosis is one of the leading potentially malignant disorders prevailing in India. A number of conservative and surgical treatment options have been suggested for this potentially malignant disorder (Arakeri and Brennan, 2013). While the role of physiotherapy has been highlighted in the conservative management, its importance in postsurgical cases to avoid scar contracture and subsequent relapse has not been given due importance in the literature. The following is a case report of a male patient surgically treated for OSMF (oral submucous fibrosis) and meticulously followed up for recalls and physiotherapy. The constant supervision and motivation for physiotherapy along with the constant assistance helped achieve satisfying results. PMID:27885345

  18. Effectiveness of Long Term Supervised and Assisted Physiotherapy in Postsurgery Oral Submucous Fibrosis Patients.

    PubMed

    Kale, S; Srivastava, N; Bagga, V; Shetty, A

    2016-01-01

    Oral submucous fibrosis is one of the leading potentially malignant disorders prevailing in India. A number of conservative and surgical treatment options have been suggested for this potentially malignant disorder (Arakeri and Brennan, 2013). While the role of physiotherapy has been highlighted in the conservative management, its importance in postsurgical cases to avoid scar contracture and subsequent relapse has not been given due importance in the literature. The following is a case report of a male patient surgically treated for OSMF (oral submucous fibrosis) and meticulously followed up for recalls and physiotherapy. The constant supervision and motivation for physiotherapy along with the constant assistance helped achieve satisfying results.

  19. The Impact of Long-Term Dental Health Education on Oral Hygiene Behavior.

    ERIC Educational Resources Information Center

    Houle, Bonnie A.

    1982-01-01

    A study evaluated the impact of five years' exposure to a dental health curriculum on the oral hygiene of fifth-grade students. Findings of the study indicate that a well-designed dental health curriculum based on cognitive and behavioral objectives can result in a greater accumulation of dental health knowledge. (JN)

  20. Long-term oral baclofen treatment in a child with cerebral palsy: electroencephalographic changes and clinical adverse effects.

    PubMed

    De Rinaldis, Marta; Losito, Luciana; Gennaro, Leonarda; Trabacca, Antonio

    2010-10-01

    Baclofen is widely used to control spasticity in children with cerebral palsy. Several publications described clinical adverse effects of baclofen oral treatment, but the effect of baclofen on seizure potentiation is still controversial. We describe a 10-year-old female patient with cerebral palsy, epilepsy, and mental retardation who developed clinical adverse effects (confusion, agitated state, insomnia, diffuse hypotonia, and hyporeflexia) and electroencephalographic (EEG) changes (quasiperiodic, generalized burst of sharp waves that take up >50% of standard EEG) during long-term oral baclofen treatment, after gradually increasing the dosage but still within the therapeutic dose. Our case showed clearly that the EEG changes in our patient, with a history of epilepsy in good control, have been induced by the baclofen increase, and we describe the possible mechanisms that could explain proconvulsive effect of baclofen.

  1. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects.

    PubMed

    Doff, Michiel H J; Veldhuis, Steffanie K B; Hoekema, Aarnoud; Slater, James J R Huddleston; Wijkstra, P J; de Bont, Lambert G M; Stegenga, Boudewijn

    2012-06-01

    The objective of this study was to assess variations in the occurrence of temporomandibular disorders (TMDs) and the risk of developing pain and function impairment of the temporomandibular complex in obstructive sleep apnea syndrome (OSAS) patients treated with either an oral appliance (mandibular advancement device) or continuous positive airway pressure (CPAP) in a 2-year follow-up study. In addition, we assessed the relationship between the mean mandibular protrusion and the frequency of wearing the appliance during follow-up with the occurrence of pain and function impairment of the temporomandibular complex. Fifty-one patients were randomized to oral appliance therapy and 52 patients to CPAP therapy. TMDs (diagnosed according to the Axis I Research Diagnostic Criteria for TMD), pain intensity and disability and mandibular function impairment were recorded at baseline, after 2 months, 1 year and 2 years of therapy. Only in the initial period of treatment the occurrence of pain-related TMDs was considerably higher (24%) in the oral appliance group compared to CPAP (6%). Oral appliance therapy furthermore resulted in more temporomandibular pain compared to CPAP (odds ratio 2.33, 95% confidence interval (1.22-4.43)). However, there were no limitations in mandibular function in both groups during the (entire) follow-up period. Although generally not serious and of transient nature, oral appliance therapy results in more pain-related TMDs in the initial period of use compared with CPAP therapy. Oral appliance therapy is associated with increased pain in the temporomandibular complex in the initial period of use. Because of the transient nature, this pain is not a reason to contra-indicate an oral appliance in OSAS patients. Moreover, TMDs and the risk of developing pain and function impairment of the temporomandibular complex appear limited with long-term oral appliance use.

  2. Pemphigus vulgaris: the manifestations and long-term management of 55 patients with oral lesions.

    PubMed

    Scully, C; Paes De Almeida, O; Porter, S R; Gilkes, J J

    1999-01-01

    Perhaps surprisingly, the manifestations and management of patients with pemphigus vulgaris and oral lesions have been detailed only infrequently. The present study has examined the clinical features, diagnosis and management of a cohort of 55 patients, including three adolescents, with pemphigus vulgaris predominantly affecting the oral mucosa. There was about a 6-month delay from the onset of symptoms until presentation for diagnosis, longer in men than in women. Patients typically had multiple lesions affecting mainly the buccal and/or palatal mucosae, and over half the patients had lesions affecting non-oral mucosal sites. Nearly one-quarter (24%) had cutaneous involvement. Most patients were otherwise healthy with no other autoimmune disorders. Classical histopathological features of pemphigus vulgaris were present in all patients, as well as IgG intraepithelial deposits in all patients tested and circulating epithelial antibodies in most. Thirty-two patients were treated in the clinic, four responding to topical immunosuppressive therapy, the remainder needing and responding, at least in part, to systemic immunosuppression. Systemic corticosteroids often with adjunctive immunosuppressives, particularly azathioprine, were required in 87% of patients. In 18% of the patients, the disease resolved in 3 months, but 76% had recalcitrant disease. Adverse effects were seen in 78%, and two patients died, at least one as a consequence of immunosuppressive therapy. It is concluded that pemphigus vulgaris affecting the oral mucosa is still diagnosed only after considerable delay because patients, especially men, present late; it has a chronic course; it is often associated with lesions in other mucosae and/or skin; it can be resistant to currently available therapies; and immunosuppressive therapy frequently produces adverse effects, occasionally lethal.

  3. Long-term experience with a low-dose oral contraceptive.

    PubMed

    Brill, K; Schnitker, J; Albring, M

    1990-12-01

    Oral contraception has proved to be the most efficient reversible method of fertility control for over 25 years. During this period, various investigations and epidemiological studies have suggested that some risks may be involved, but, on the other hand, a number of non-contraceptive benefits have become obvious. The results of these investigations were taken into account when new formulations had to be developed, with an aim to improving hormonal fertility control with regard to its tolerance, cycle control, and impact on metabolism. Since then, the objective of research has been to contrive new hormonal contraceptives which ensure safety to the largest possible extent, from a medical point of view, for the sake of the patient, without affecting contraceptive effectiveness. The aim to reduce side-effects connected with the use of oral contraception, as well as to lower the risks possibly involved, has obviously been achieved by extensive research. Both by devising a new substance and reducing doses, the criteria of modern low-dose oral contraception have been met, as has become evident in the course of the clinical experience gathered with Femovan.

  4. Effects of dietary L-arginine on the reactivity of canine coronary arteries.

    PubMed

    Ray, E C; Landis, M E; Miller, V M

    1999-01-01

    Experiments were designed to determine the effects of supplemental dietary L-arginine on the endothelial and smooth muscle function of canine coronary arteries. One group of dogs was fed the standard laboratory chow while another group was supplemented with 250 mg/kg per day L-arginine. All dogs had undergone bilateral reversed interposition saphenous vein grafting and received 325 mg/day oral aspirin. After 5 weeks of arginine feeding, left circumflex coronary arteries were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers. Concentration-response curves were obtained to L-arginine, UK-14,304 (alpha2-adrenergic agonist) and A23187 (calcium ionophore) in the absence and presence of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium (TEA) alone or in combination. Serum concentrations of L-arginine increased by about 20% following 2 weeks of arginine feeding and remained elevated throughout the study. In rings with and without endothelium contracted with prostaglandin F2alpha, L-arginine caused concentration-dependent contractions in rings from control animals but no significant change in tension in rings from arginine-fed animals. Contractions to L-arginine in control animals were reduced by either L-NMMA or TEA. Endothelium-dependent relaxations to the alpha2-adrenergic agonist were decreased with arginine feeding while relaxations to the calcium ionophore and the endothelium-derived factor nitric oxide were similar among groups. Relaxations to UK-14,304 were reduced by L-NMMA in both groups but by TEA only in rings from control animals. These results suggest that dietary supplementation with L-arginine modifies reactivity of endothelium and smooth muscle by at least two mechanisms: one associated with activation of potassium channels and the other with receptor-coupled release of nitric oxide.

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

    PubMed Central

    Gay-Escoda, Cosme; Pérez-Álvarez, Débora; Camps-Font, Octavi

    2016-01-01

    Background 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. Material and Methods 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. Results 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). Conclusions 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. Key words:HIV infection, dental implants, oral implantology, complications, peri-implantitis, peri-implant diseases. PMID:26946205

  6. Long-term use of oxcarbazepine oral suspension in childhood epilepsy: open-label study.

    PubMed

    Rufo-Campos, Miguel; Casas-Fernández, Carlos; Martínez-Bermejo, Antonio

    2006-06-01

    Studies designed specifically for the pediatric population are needed to assess the tolerability and safety of the new antiepileptic drugs. The purpose of this study was to document the safety, ease of dosing, and acceptance of oxcarbazepine oral suspension in pediatric patients in monotherapy and polytherapy. A prospective, multicenter, open-label study was conducted at the neurology services of three pediatric university hospitals over 12 months. After obtaining signed informed consent, we enrolled a series of 62 patients with epilepsy aged between 2 months and 14 years who began oxcarbazepine treatment in monotherapy or in combination with other antiepileptic drugs to assess the seizure frequency, safety (adverse events), and acceptance of the pharmaceutical form by the patient's family. Fifty patients (80.6%) reduced seizures by at least 50%, 44 (71%) saw a reduction in seizure frequency of over 75%, and 29 (46.8%) were seizure free at the end of the study. The difference in the number of seizures before and after the study was statistically significant, both overall and by type of pathology. Adverse events occurred in four patients (6.4%) and required withdrawal of the drug in two cases (skin rash); three patients (4.8%) withdrew for inefficacy. Five patients (8.1%) withdrew from the treatment. We concluded that, in this series of patients, oxcarbazepine in oral suspension form was seen to help reduce seizure frequency, to have few side effects, and to be accepted by parents and patients.

  7. L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides.

    PubMed

    Schulze, Friedrich; Glos, Sabrina; Petruschka, Dörte; Altenburg, Christiane; Maas, Renke; Benndorf, Ralf; Schwedhelm, Edzard; Beil, Ulrich; Böger, Rainer H

    2009-05-01

    We recently noticed a possible triglyceride-lowering effect during dietary supplementation with L-arginine. The major limitation of prior studies on L-arginine, however, was that triglyceride levels were not the primary end point, and patients were not necessarily hypertriglyceridemic. Therefore, we conducted a 2-arm, randomized, double-blind study in 33 hypertriglyceridemic patients to investigate the hypothesis that oral L-arginine may lower serum triglyceride levels in hypertriglyceridemic patients on and off statins. The study consisted of a 6-week run-in phase, 6 weeks of treatment with L-arginine (n = 22, 1.5 g bid) or placebo (n = 11), and a 6-week extension period where simvastatin (20 mg qd) was added. All patients received dietary advice during each study visit. Routine and lipid laboratory parameters were determined in the local routine clinical laboratory. Treatment with L-arginine alone had no effects on serum lipids compared to placebo. The combination of L-arginine with simvastatin led to a significantly stronger reduction in triglycerides compared to placebo plus simvastatin (-140.5 +/- 149.2 mg/dL vs -56.1 +/- 85.0 mg/dL; P = .048). In addition, we found simvastatin-induced increases in aspartate transaminase and fibrinogen to be attenuated by L-arginine as compared to placebo. We conclude from our data that L-arginine enhances the effects of simvastatin on lipid metabolism, but it has no triglyceride-lowering effects when given alone.

  8. Long-Term High-dose Oral Morphine in Phantom Limb Pain with No Addiction Risk

    PubMed Central

    Kumar, Vinod; Garg, Rakesh; Bharati, Sachidanand Jee; Gupta, Nishkarsh; Bhatanagar, Sushma; Mishra, Seema; Balhara, Yatan Pal Singh

    2015-01-01

    Chronic phantom limb pain (PLP) is a type of neuropathic pain, which is located in the missing/amputated limb. Phantom pain is difficult to treat as the exact basis of pain mechanism is still unknown. Various methods of treatment for PLP have been described, including pharmacological (NSAIDs, opioids, antiepileptic, antidepressants) and non-pharmacological (TENS, sympathectomy, deep brain stimulation and motor cortex stimulation). Opioids are used for the treatment of neuropathic pain and dose of opioid is determined based on its effect and thus there is no defined ceiling dose for opioids. We report a case where a patient receiving high-dose oral morphine for chronic cancer pain did not demonstrate signs of addiction. PMID:25709194

  9. Long-term oral administration of hop flower extracts mitigates Alzheimer phenotypes in mice.

    PubMed

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the "amyloid hypothesis" has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the "amyloid hypothesis", we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the "amyloid hypothesis", and indicate that Hop extract is a promising candidate for an effective prophylactic for AD.

  10. Long-Term Oral Administration of Hop Flower Extracts Mitigates Alzheimer Phenotypes in Mice

    PubMed Central

    Sasaoka, Norio; Sakamoto, Megumi; Kanemori, Shoko; Kan, Michiru; Tsukano, Chihiro; Takemoto, Yoshiji; Kakizuka, Akira

    2014-01-01

    Coincident with the expanding population of aged people, the incidence of Alzheimer disease (AD) is rapidly increasing in most advanced countries. At present, no effective prophylactics are available. Among several pathological mechanisms proposed for AD, the “amyloid hypothesis” has been most widely accepted, in which accumulation or deposition of Aβ is considered to be the initial event. Thus, prevention of Aβ production would be an ideal strategy for the treatment or prevention of AD. Aβ is produced via the proteolytic cleavage of its precursor protein, APP (amyloid precursor protein), by two different enzymes, β and γ-secretases. Indeed, inhibitors against either or both enzymes have been developed and tested for clinical efficacy. Based on the “amyloid hypothesis”, we developed a luciferase-based screening method to monitor γ-secretase activity, screened more than 1,600 plant extracts, most of which have long been used in Chinese medicine, and observed that Hop extracts significantly inhibit Aβ production in cultured cells. A major component of the inhibitory activity was purified, and its chemical identity was determined by NMR to be Garcinielliptone HC. In vivo, oral administration of Hop extracts to AD model mice decreased Aβ depositions in the cerebral cortex of the parietal lobe, hippocampus, and artery walls (amyloid angiopathy) in the brains. In a Morris water maze test, AD model mice that had daily consumed Hop extracts in their drinking water showed significant mitigation of memory impairment at ages of 9 and 12 months. Moreover, in the open field test oral administration of Hop extracts also prevented an emotional disturbance that appeared in the AD mice at 18 months. Despite lifelong consumption of Hop extracts, no deleterious side effects were observed at any age. These results support the “amyloid hypothesis”, and indicate that Hop extract is a promising candidate for an effective prophylactic for AD. PMID:24489866

  11. Disabled patients and oral health in Rome, Italy: long-term evaluation of educational initiatives

    PubMed Central

    Avenali, Laura; Guerra, Fabrizio; Cipriano, Luigi; Corridore, Denise; Ottolenghi, Livia

    2012-01-01

    Summary This study is concerned with the educational intervention layout proposed as a possible answer for the disparities in healthcare services for disabled persons. Material and methods The data sampling was performed on individuals in Rome, affected by psychophysical disabilities, living in residential care facilities. Participants were randomly divided into two groups: Study and Control Group, consisting of patients who did or did not participate in the Educational Phase. All the caregivers participated in an educational course. Screening period: September 2008 – March 2009. Examinations were performed using Visible Plaque Index (VPI), Gingival Bleeding Index (GBI) and Microbiological Analysis. Results The total number of patients utilized for the study was 36 (18 in each group). The final sample amounted to 70% (14/20) in the Study Group and to 75% (15/20) in the Control Group. In both examined groups Oral Hygiene, Gingival Health State and Microbiological Analysis show an overall improvement of the indices, compared with the initial status, mostly at a follow-up after 4 weeks. However, Study Group show a significantly better improvement. Conversely, after 6 months the overall clinical indices worsened again. Conclusion The difference in the significant improvements of the groups, even if only over a short-time evaluation, endorses that the participation of the patients as well as tutors in the educational phase is an effective strategy for the short-term. PMID:22545186

  12. Th17 cells confer long term adaptive immunity to oral mucosal Candida albicans infections

    PubMed Central

    Hernández-Santos, Nydiaris; Huppler, Anna R.; Peterson, Alanna C.; Khader, Shabaana A.; McKenna, Kyle C.; Gaffen, Sarah L.

    2012-01-01

    Oropharyngeal candidiasis (OPC) is an opportunistic infection caused by Candida albicans. Despite its prevalence, little is known about C. albicans-specific immunity in the oral mucosa. Vaccines against Candida generate both Th1 and Th17 responses, and considerable evidence implicates IL-17 in immunity to OPC. However, IL-17 is also produced by innate immune cells that are remarkably similar to Th17 cells, expressing the same markers and localizing to similar mucosal sites. To date, the relative contribution(s) of Th1, Th17 and innate IL-17-producing cells in OPC have not been clearly defined. Here, we sought to determine the nature and function of adaptive T cell responses to OPC, using a new recall infection model. Mice subjected to infection and re-challenge with Candida mounted a robust and stable antigen specific IL-17 response in CD4+ but not CD8+ T cells. There was little evidence for Th1 or Th1/Th17 responses. The Th17 response promoted accelerated fungal clearance, and Th17 cells could confer protection in Rag1−/− mice upon adoptive transfer. Surprisingly, CD4 deficiency did not cause OPC, but was instead associated with compensatory IL-17 production by Tc17 and CD4-CD8-CD3+ cells. Therefore, classic CD4+Th17 cells protect from OPC, but can be compensated by other IL-17-producing cells in CD4-deficient hosts. PMID:23250275

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

    PubMed Central

    2017-01-01

    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. PMID:28367261

  14. Long-term physical inactivity and oral health in Finnish adults with intellectual disability.

    PubMed

    Karjalainen, Sára; Vanhamäki, Milla; Kanto, Dunja; Kössi, Liisa; Sewón, Liisi; Salo, Matti

    2002-01-01

    Physical inactivity is prevalent among patients with intellectual disability. Because little is known about the oral effects of poor mobility, we reviewed the medical and dental charts of institutionalized dentate patients (n = 214; 40.2 years +/- 12.1) of the Special Welfare District of Southwestern Finland. The number of decayed, missing, and filled teeth (DMFT), the number of retained teeth, dental treatment visits, and the type of the first treatment visit were recorded. Physical activity was good in 55% and severely reduced or completely absent in 45% of the patients. The degree of intellectual disability was mild or moderate in 40% and severe or profound in 60% of the patients. The walking patients weighed more (64.3 (19.6) versus 44.4 (14.4) kg; P< 0.001), had fewer secondary diagnoses (1.4 (1.3) versus 2.2 (1.4); P< 0.001), fewer daily medications (4.0 (2.1) versus 4.8 (2.4); P< 0.02), higher DMFT scores (18.5 (8.2) versus 14.8 (9.2); P < 0.05), and more dental treatment visits (2.7 (2.4) versus 2.0 (1.3); P< 0.03) than patients with poor physical activity. Periodontal treatment given as the primary type of dental care was more common among subjects with poor mobility than among those with good motor activity (P < 0.002). Poor physical activity was related to better dental health, higher need for periodontal therapy, and fewer dental visits than in patients with good motor activity.

  15. Natural vitamin E alpha-tocotrienol: retention in vital organs in response to long-term oral supplementation and withdrawal.

    PubMed

    Patel, Viren; Khanna, Savita; Roy, Sashwati; Ezziddin, Omar; Sen, Chandan K

    2006-07-01

    The natural vitamin E tocotrienol (TCT) possesses biological properties not shared by tocopherols (TCP). Nanomolar alpha-TCT, not alpha-TCP, is potently neuroprotective (JBC 275:13049; 278:43508; Stroke 36:2258). The report that the affinity of TTP to bind (alpha-TCT is an order of magnitude lower than that for alpha-TCP questions the bioavailability of orally taken TCT to tissues. Oral supplementation of TCT for 3 years in nine generations of female and male rat was studied. Ten vital organs were examined. To gain insight into the turnover of alpha-TCT in tissues, a subset of supplemented rats was moved to vitamin E deficient diet for 7 weeks. Orally supplemented alpha-TCT was delivered to all vital organs including the brain and spinal cord in significant amounts. In organs such as the skin, adipose and gonads the maximum level of alpha-TCT achieved in response to supplementation was folds higher than baseline values of alpha-TCP in rats maintained on laboratory chow. Females had higher levels of alpha-TCT compared to matched tissues of corresponding males. To gain insight into how quickly alpha-TCT is metabolized in the tissues, washout of alpha-TCT from vital organs was examined. alpha-TCT accumulated in vital organs over more than 2 years was almost completely lost in less than 2 months when the supplementation was stopped. This is in sharp contrast with findings related to alpha-TCP retention. The ability of long-term oral supplementation to maintain and elevate alpha-TCT levels in vital organs together with the rapid elimination of the intact vitamin from all organs studied underscores the need for continuous oral supplementation of TCT.

  16. [Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension].

    PubMed

    Kurzyna, Marcin; Florczyk, Michał; Fijałkowska, Anna; Kuca, Paweł; Szewczyk, Grzegorz; Burakowski, Janusz; Kober, Jarosław; Sikora, Jarosław; Wawrzyńska, Liliana; Szturmowicz, Monika; Tomkowskil, Witold; Torbicki, Adam

    2004-04-01

    Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.

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

    PubMed

    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.

  18. Relationship between serum arginase I and l-arginine or exhaled nitric oxide in asthma.

    PubMed

    Ogino, Keiki; Obase, Yasushi; Ito, Tatsuo; Fujimura, Masaki; Eguchi, Eri; Kubo, Masayuki; Nagaoka, Kenjiro; Nakamura, Hiroyuki

    2016-01-01

    The relationship between serum arginase I and serum l-arginine or fractional exhaled nitric oxide (FENO) was evaluated cross-sectionally in asthmatic patients. No sex difference was observed in the serum mean levels of arginase I and l-arginine or FENO. Arginase I and FENO were higher in patients 60 or younger years than in those over 60 years. Asthmatic patients were divided into three groups: no steroid therapy, inhalation steroid therapy, and oral steroid therapy. Arginase I, FENO and high-sensitivity-C-reactive protein (hs-CRP) were significantly lower in the inhalation steroid therapy group than in the no steroid therapy group. Correlations were observed between arginase I and FENO, l-arginine, hs-CRP, WBC, and age, and also between FENO and IgE, WBC, and age. A logistic regression analysis revealed the positive association of arginase I with FENO, and the negative association of l-arginine. FENO was positively associated with arginase I and IgE. These results indicated that serum arginase I might influence serum levels of l-arginine and FENO, and that IgE might influence FENO in asthmatic patients.

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

    SciTech Connect

    Yu, Cheng-Chia; Chang, Yu-Chao

    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

  20. Oral toxicity of 1,2-dichloropropane: Acute, short-term, and long-term studies in rats

    SciTech Connect

    Bruckner, J.V.; MacKenzie, W.F.; Ramanathan, R.; Muralidhara, S.; Kim, H.J.

    1989-01-01

    The investigation characterized the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia.

  1. The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors.

    PubMed

    Zhang, Ding; Zhang, Zheyu; Liu, Yayun; Chu, Maoquan; Yang, Chengyu; Li, Wenhao; Shao, Yuxiang; Yue, Yan; Xu, Rujiao

    2015-11-01

    Reduced graphene oxide (rGO), a carbon-based nanomaterial, has enormous potential in biomedical research, including in vivo cancer therapeutics. Concerns over the toxicity remain outstanding and must be investigated before clinical application. The effect of rGO exposure on animal behaviors, such as learning and memory abilities, has not been clarified. Herein, we explored the short- and long-term effects of orally administered rGO on mouse behaviors, including general locomotor activity level, balance and neuromuscular coordination, exploratory and anxiety behaviors, and learning and memory abilities using open-field, rotarod, and Morris water maze tests. Compared with mice administered buffer-dispersed mouse chow or buffer alone, mice receiving a high dose of small or large rGO nanosheets showed little change in exploratory, anxiety-like, or learning and memory behaviors, although general locomotor activity, balance, and neuromuscular coordination were initially affected, which the mechanisms (e.g. the influence of rGO exposure on the activity of superoxide dismutase in mouse serum) were discussed. The results presented in this work look to provide a deep understanding of the in vivo toxicity of rGO to animals, especially its effect on learning and memory and other behaviors.

  2. L-arginine-induced experimental pancreatitis

    PubMed Central

    Hegyi, Péter; Jr, Zoltán Rakonczay; Sári, Réka; Góg, Csaba; Lonovics, János; Takács, Tamás; Czakó, László

    2004-01-01

    Despite medical treatment, the lethality of severe acute pancreatitis is still high (20%-30%). Therefore, it is very important to find good animal models to characterise the events of this severe disease. In 1984, Mizunuma et al[1] developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats. This non-invasive model is highly reproducible and produces selective, dose-dependent acinar cell necrosis. Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis, but it is also excellent to observe and influence the time course changes of the disease. By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis. Unfortunately, the reviews about acute experimental pancreatitis usually did not discuss this model. Therefore, the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis. PMID:15237423

  3. Antihypertensive Properties of a Pea Protein Hydrolysate during Short- and Long-Term Oral Administration to Spontaneously Hypertensive Rats.

    PubMed

    Girgih, Abraham T; Nwachukwu, Ifeanyi D; Onuh, John O; Malomo, Sunday A; Aluko, Rotimi E

    2016-05-01

    This study investigated short-term (24 h) and long-term (5 wk) systolic blood pressure (SBP)-lowering effects in spontaneously hypertensive rats (SHR) of a 5 kDa membrane pea protein hydrolysate permeate (PPH-5) produced through thermoase hydrolysis of pea protein isolate (PPI). Amino acid analysis showed that the PPH-5 had lower contents of sulfur-containing amino acids than the PPI. Size-exclusion chromatography indicated mainly low molecular weight (<10 kDa) peptides in PPH-5 but not in the PPI. The PPH-5 had renin and angiotensin converting enzyme inhibition IC50 values of 0.57 and 0.10 mg/mL (P < 0.05), respectively, and consisted mainly of peptides with 2 to 6 amino acids. Mass spectrometry analysis revealed mainly hydrophilic tetrapeptide sequences. After a single oral administration (100 mg/kg body weight) to SHR, the unheated PPI showed weakest (P < 0.05) SBP-lowering effect with a -4 mm Hg maximum when compared to -25 mm Hg for heat-treated PPI and -36 mm Hg for PPH-5. Incorporation of the PPH-5 as 0.5% or 1% (w/w) casein substitute in the SHR diet produced maximum SBP reductions of -22 or -26 mm Hg (P < 0.05), respectively after 3 wk. In comparison, the unhydrolyzed PPI produced a maximum SBP reduction of -17 mm Hg also after 3 wk. Potency of the pea products decreased in the 4th and 5th wk, though SBP values of the treated rats were still lower than the untreated control. We conclude that the antihypertensive potency of PPH-5 may have been due to the presence of easily absorbed hydrophilic peptides.

  4. Effects of dietary L-arginine intake on cardiorespiratory and metabolic adaptation in athletes.

    PubMed

    Bescós, Raul; Gonzalez-Haro, Carlos; Pujol, Pere; Drobnic, Franchek; Alonso, Eulalia; Santolaria, Maria Luisa; Ruiz, Olga; Esteve, Marc; Galilea, Pedro

    2009-08-01

    To assess the effect of diet enrichment with L-arginine or supplementation at high doses on physiological adaptation during exercise, 9 athletes followed 3 different diets, each over 3 consecutive days, with a wash-out period of 4 d between training sessions: control diet (CD), 5.5 +/- 0.3 g/d of L-arginine; Diet 1 (rich in L-arginine food), 9.0 +/- 1.1 g/d of L-arginine; and Diet 2 (the same as CD but including an oral supplement of 15 g/d), 20.5 +/- 0.3 g/d of L-arginine. Plasma nitrate levels of each participant were determined on the day after each treatment. Participants performed a submaximal treadmill test (initial speed 10-11 km/hr, work increments 1 km/hr every 4 min until 85-90% VO2max, and passive recovery periods of 2 min). Oxygen uptake and heart rate were monitored throughout the test. Blood lactate concentration ([La-]b) was determined at the end of each stage. Repeated-measures ANOVA and paired Student's t tests were used to compare the various physiological parameters between diets. The level of significance was set at p < .05. [La-]b showed a significant effect at the 5-min time point between CD and Diet 2 (CD 3.0 +/- 0.5 mM, Diet 2 2.5 +/- 0.5 mM, p = .03), but this tendency was not found at higher exercise intensities. No significant differences were observed in any of the cardiorespiratory or plasma nitrate levels. In conclusion, dietary L-arginine intake on the days preceding the test does not improve physiological parameters during exercise.

  5. L-Arginine and Alzheimer's Disease

    PubMed Central

    Yi, Jing; Horky, Laura L.; Friedlich, Avi L.; Shi, Ying; Rogers, Jack T.; Huang, Xudong

    2009-01-01

    Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration and loss of cognitive and memory functions. Although the exact causes of AD are still unclear, evidence suggests that atherosclerosis, redox stress, inflammation, neurotransmitter dysregulation, and impaired brain energy metabolism may all be associated with AD pathogenesis. Herein, we explore a possible role for L-arginine (L-arg) in AD, taking into consideration known functions for L-arg in atherosclerosis, redox stress and the inflammatory process, regulation of synaptic plasticity and neurogenesis, and modulation of glucose metabolism and insulin activity. L-arg, a precursor of nitric oxide and polyamine, exhibits multiple functions in human health and may play a prominent role in age-related degenerative diseases such as AD. PMID:19079617

  6. Drug-Containing Gelatin Treats as an Alternative to Gavage for Long-Term Oral Administration in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Zhang, Shuang; Ye, Bin; Zeng, Li; Chen, Younan; He, Sirong; Wang, Chengshi; Li, Xinli; Zhao, Jiuming; Shi, Meimei; Wang, Li; Li, Hongxia; Cheng, Jingqiu; Wang, Wei; Lu, Yanrong

    2012-01-01

    Long-term oral administration of immunosuppressive agents to transplanted rhesus monkeys (Macaca mulatta) is one of the major challenges in such studies. To avoid the drawbacks of gavage, we tested an alternative method for oral dosing of sirolimus in rhesus monkeys by adding sirolimus, a commonly used immunosuppressant, to gelatin to create drug-containing gelatin ‘treats’ that our macaques would accept voluntarily. We evaluated the oral bioequivalence of the oral solution and drug-containing gelatin and assayed the whole-blood levels of sirolimus after long-term drug delivery. We found that time to peak concentration but not peak concentration itself or the area under the time–concentration curve differed between the 2 groups. Although the maximal concentration data did not fit the condition of bioequivalence, those for the time–concentration curves from 0 to 24 h and from 0 h to infinity did; therefore the extent of sirolimus absorption did not differ significantly between the 2 formulations. The sirolimus levels for long-term drug delivery were equivalent at 2.97 ± 1.91 ng/mL in the gelatin group and 3.13 ± 2.03 ng/mL in the solution group. The gelatin dosing technique we describe here is convenient and effective for oral administration of sirolimus in rhesus monkeys and likely can be adapted for other drugs. PMID:23294893

  7. Long-Term Effectiveness of Parent Education Using the “Baby Oral Health” Model on the Improvement of Oral Health of Young Children

    PubMed Central

    Kulkarni, Gajanan V.

    2013-01-01

    Purpose. To determine the long-term effectiveness of comprehensive education given to parents and caregivers with respect to the incidence of preventable oral diseases, utilization of dental services, and retention of knowledge related to oral health. Methods. Group presentations on oral health were conducted for caregivers of infants (n = 161) using an interactive audio-visual aid. Followup occurred at 18 months. A comparison group (n = 181) was enrolled from the same community groups. Chi-square and Fisher's exact tests were used to analyze findings. Results. There was a difference in caries incidence, knowledge levels of caregivers, and utilization of dental services (P < 0.05) when comparing the SGB to the SGFU. Conclusions. One-time exposure to parent education using a comprehensive interactive audio-visual aid has an effect on reducing caries incidence and increasing dental utilization. While most knowledge is retained by parents, there is some attrition in the information retained over an 18-month time period. This emphasizes the importance of repeated reinforcement of the same concepts over a shorter time span. PMID:24319460

  8. Metabolic engineering of Corynebacterium glutamicum for L-arginine production.

    PubMed

    Park, Seok Hyun; Kim, Hyun Uk; Kim, Tae Yong; Park, Jun Seok; Kim, Suok-Su; Lee, Sang Yup

    2014-08-05

    L-arginine is an important amino acid for diverse industrial and health product applications. Here we report the development of metabolically engineered Corynebacterium glutamicum ATCC 21831 for the production of L-arginine. Random mutagenesis is first performed to increase the tolerance of C. glutamicum to L-arginine analogues, followed by systems metabolic engineering for further strain improvement, involving removal of regulatory repressors of arginine operon, optimization of NADPH level, disruption of L-glutamate exporter to increase L-arginine precursor and flux optimization of rate-limiting L-arginine biosynthetic reactions. Fed-batch fermentation of the final strain in 5 l and large-scale 1,500 l bioreactors allows production of 92.5 and 81.2 g l(-1) of L-arginine with the yields of 0.40 and 0.35 g L-arginine per gram carbon source (glucose plus sucrose), respectively. The systems metabolic engineering strategy described here will be useful for engineering Corynebacteria strains for the industrial production of L-arginine and related products.

  9. Fluorometric enzymatic assay of L-arginine

    NASA Astrophysics Data System (ADS)

    Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

    2017-01-01

    The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

  10. Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy

    PubMed Central

    2009-01-01

    Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a

  11. Inhibition by memantine of the development of persistent oral dyskinesias induced by long-term haloperidol treatment of rats.

    PubMed Central

    Andreassen, O. A.; Aamo, T. O.; Jøorgensen, H. A.

    1996-01-01

    1. Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if neuroleptic-induced excessive stimulation of striatal glutamate receptors may underlie TD development, the effect of the NMDA antagonist, memantine (1-amino-3,5-dimethyladamantane), was studied in a rat model of TD. 2. In an acute experiment, six groups of rats were treated daily for 1 week with either vehicle or memantine 20 or 40 mg kg-1 day-1, and on the seventh day they received one injection of either haloperidol 1.0 mg kg-1 i.p. or saline i.p. In a subsequent long-term experiment lasting 20 weeks, the same treatment was continued, except that haloperidol was injected i.m. as decanoate (38 mg kg-1 every 4 weeks) and control rats received sesame oil. The behaviour was videotaped and scored at intervals during both experiments, and for 16 weeks after cessation of the long-term treatment. 3. In the acute experiment, haloperidol decreased motor activity and memantine increased moving and tended to attenuate the immobility induced by haloperidol. Memantine also enhanced the haloperidol-induced increase in the putative TD-analogue vacuous chewing movements (VCM). 4. In the long-term experiment, the most marked effect of haloperidol was a gradual increase in VCM and the increase persisted significantly for 12 weeks after cessation of treatment. Memantine dose-dependently increased VCM and moving during long-term treatment. However, only one week after stopping treatment, both these effects of memantine disappeared. In contrast to rats previously treated with haloperidol alone, rats co-treated with memantine (both doses) and haloperidol had VCM at the level of controls two weeks after stopping treatment. The blood levels of drugs were within the therapeutic range achieved in human subjects. 5. These results suggest that long-lasting changes induced by haloperidol are prevented by memantine, which supports the theory that excessive NMDA receptor stimulation

  12. Effects of L-arginine and NG-nitro L-arginine methyl ester (L-NAME) on ischemia/reperfusion injury of skeletal muscle, small and large intestines.

    PubMed

    Krauss, Hanna; Sosnowski, Przemyslaw; Biczysko, Maciej; Biczysko, Wieslawa; Majewski, Przemyslaw; Jablecka, Anna; Miskowiak, Bogdan; Smolarek, Iwona; Konwerska, Aneta; Ignys, Iwona; Micker, Maciej

    2011-02-28

    This study analyzed the effects of L-arginine and non-specific nitric oxide (NO) synthase blocker (L-NAME) on structural and metabolic changes in experimental ischemia/reperfusion injury in the rat. Histopathological evaluation of rat tissues after reperfusion was also performed. The animals were divided into four groups: [1] nonischemic control, [2] ischemia 4 hrs/repefusion 30, 60, 120 min, [3] ischemia/reperfusion after L-arginine administration, [4] ischemia/reperfusion, after L-arginine, and L-NAME. L-arginine (500 mg/kg) and L-NAME (75 micromol/rat/day) were administrated orally for 5 days before experiment. Concentrations of free radicals, CD-62P, CD-54 and malonyl dialdehyde (MDA) in tissues, and MDA and NO levels in sera were determined. Free radical levels significantly increased in reperfused skeletal muscle, small and large intestines. In large bowel, reperfusion increased MDA levels and evoked a rise of endotoxin level while NO levels decreased. Histological studies showed an increase in the number of lymphocytes in both intestines. Administration of L-arginine reduced leukocyte adherence associated with ischemia-repefusion injury, decreased the levels of free radicals and MDA in the examined tissues, and inhibited the release of endotoxins into blood. L-arginine-treated animals showed higher serum NO levels and reduced leukocyte bowel infiltration. Concomitant L-NAME administration reduced serum NO and tissue free radical [corrected] levels, but did not affect intestinal leukocyte infiltration. L-arginine could ameliorate intestinal ischemia/reperfusion injury and constitute a possible protective mechanism by decreasing neutrophil-endothelial interactions, stimulating free radical scavenging and reducing lipid peroxidation.

  13. Regulation of immune responses by L-arginine metabolism.

    PubMed

    Bronte, Vincenzo; Zanovello, Paola

    2005-08-01

    L-Arginine is an essential amino acid for birds and young mammals, and it is a conditionally essential amino acid for adult mammals, as it is important in situations in which requirements exceed production, such as pregnancy. Recent findings indicate that increased metabolism of L-arginine by myeloid cells can result in the impairment of lymphocyte responses to antigen during immune responses and tumour growth. Two enzymes that compete for L-arginine as a substrate - arginase and nitric-oxide synthase - are crucial components of this lymphocyte-suppression pathway, and the metabolic products of these enzymes are important moderators of T-cell function. This Review article focuses on the relevance of L-arginine metabolism by myeloid cells for immunity under physiological and pathological conditions.

  14. Long-term outcomes of a dental postbaccalaureate program: increasing dental student diversity and oral health care access.

    PubMed

    Wides, Cynthia D; Brody, Harvey A; Alexander, Charles J; Gansky, Stuart A; Mertz, Elizabeth A

    2013-05-01

    The University of California, San Francisco School of Dentistry established the Dental Postbaccalaureate Program in 1998 to provide reapplication assistance to students from economically and/or educationally disadvantaged backgrounds who were previously denied admission to dental school. The goals were to increase diversity in the dental school student population and improve access to dental services for underserved populations. This article assesses the program's short-, mid-, and long-term outcomes and is the first to examine long-term practice patterns after a dental postbaccalaureate program. Data collected on all participant (n=94) demographics, pre/post-program DAT scores, and post-program dental school admission results were used to assess short- and mid-term outcomes. Long-term outcomes and practice patterns were assessed using results of a census survey administered between 2009 and 2011 to the participants who had completed dental school and been in practice for at least two years (n=57). The survey had a response rate of 93 percent (n=53). Descriptive statistical techniques were used to examine the responses and to compare them to U.S. Census Bureau data and nationally available practice data for new dental graduates. Program participants' DAT scores improved by an average of two points, and 98 percent were accepted to dental school. All survey respondents were practicing dentistry, and 81 percent reported serving underserved populations. These participants treat more Medicaid recipients than do most dentists, and their patient population is more diverse than the general population. The outcomes demonstrate that the program's graduates are increasing diversity in the dental student population and that their practices are providing access to care for underserved populations.

  15. Anti-stress and Adaptogenic Activity of l-Arginine Supplementation

    PubMed Central

    2005-01-01

    In the present study, oral supplementation of l-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C)–hypoxia (428 mmHg)–restraint (C-H-R) animal model. A dose-dependent study of l-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C) during C-H-R exposure and its recovery to Trec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effective l-arginine dose, were measured in rats on attaining Trec 23°C and Trec 37°C. The least effective adaptogenic dose of l-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attaining Trec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (Trec 37°C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH. l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attaining Trec 23°C during C-H-R exposure and on recovery to Trec 37°C. The results suggested that l-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia. PMID:15841283

  16. Alteration in plasma corticosterone levels following long term oral administration of lead produces depression like symptoms in rats.

    PubMed

    Haider, Saida; Saleem, Sadia; Tabassum, Saiqa; Khaliq, Saima; Shamim, Saima; Batool, Zehra; Parveen, Tahira; Inam, Qurat-ul-ain; Haleem, Darakhshan J

    2013-03-01

    Lead toxicity is known to induce a broad range of physiological, biochemical and behavioral dysfunctions that may result in adverse effects on several organs, including the central nervous system. Long-term exposure to low levels of lead (Pb(2+)) has been shown to produce behavioral deficits in rodents and humans by affecting hypothalamic-pituitary-adrenal (HPA) axis. These deficits are thought to be associated with altered brain monoamine neurotransmission and due to changes in glucocorticoids levels. This study was designed to investigate the effects of Pb(2+)exposure on growth rate, locomotor activity, anxiety, depression, plasma corticosterone and brain serotonin (5-HT) levels in rats. Rats were exposed to lead in drinking water (500 ppm; lead acetate) for 5 weeks. The assessment of depression was done using the forced swimming test (FST). Estimation of brain 5-HT was determined by high-performance liquid chromatography with electrochemical detection. Plasma corticosterone was determined by spectrofluorimetric method. The present study showed that long term exposure to Pb(2+) significantly decreased the food intake followed by the decrease in growth rate in Pb(2+)exposed rats as compared to control group. No significant changes in open field activity were observed following Pb(2+)exposure while significant increase in anxiogenic effect was observed. Increased plasma corticosterone and decreased 5-HT levels were exhibited by Pb(2+)exposed rats as compared to controls. A significant increase in depressive like symptoms was exhibited by Pb(2+)exposed rats as compared to control rats. The results are discussed in the context of Pb(2+) inducing a stress-like response in rats leading to changes in plasma corticosterone and brain 5-HT levels via altering tryptophan pyrrolase activity.

  17. Long-Term Care

    MedlinePlus

    ... this page please turn Javascript on. Long-Term Care What Is Long-Term Care? Long-term care involves a variety of services ... the Escape (Esc) button on your keyboard.) Most Care Provided at Home Long-term care is provided ...

  18. Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin.

    PubMed

    Salkovic-Petrisic, Melita; Osmanovic-Barilar, Jelena; Knezovic, Ana; Hoyer, Siegfried; Mosetter, Kurt; Reutter, Werner

    2014-02-01

    Basic and clinical research has demonstrated that dementia of sporadic Alzheimer's disease (sAD) type is associated with dysfunction of the insulin-receptor (IR) system followed by decreased glucose transport via glucose transporter GLUT4 and decreased glucose metabolism in brain cells. An alternative source of energy is d-galactose (the C-4-epimer of d-glucose) which is transported into the brain by insulin-independent GLUT3 transporter where it might be metabolized to glucose via the Leloir pathway. Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg/kg/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg/kg/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD.

  19. Osteonecrosis of the Torus Palatinus in the Setting of Long-Term Oral Bisphosphonate Use--A Case Report.

    PubMed

    Ryan, Joshua L; Larson, Eric

    2016-01-01

    Bisphosphonates are medications used orally and intravenously for a variety of conditions including cancer metastatic to bone, hypercalcemia of malignancy, Paget's disease and osteoporosis. Osteonecrosis of the jaw has been related to bisphosphonate use. Osteonecrosis of the jaw most commonly occurs in the setting of intravenous bisphosphonate use and concomitant dental work or trauma. Oral bisphosphonates have much less risk of osteonecrosis of the jaw. We present an interesting case of a patient on an oral bisphosphonate for an extended period of time (nine years), with a torus palatinus, who burned her palate while eating a slice of pizza. Over six months later, she presented with an area of denuded bone and diagnosis consistent with osteonecrosis of the torus palatinus.

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

    PubMed Central

    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

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

    PubMed

    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.

  2. Dietary L-arginine and cutaneous wound healing.

    PubMed

    Naderpour, Masoud; Rad, Jafar Soleimani; Ayat, Esmail; Mesgari, Mehran; Farahani, Ramin M; Roshangar, Leila; Tubbs, R Shane; Shoja, Mohammadali M

    2008-01-01

    Skin wound healing has been the subject of extensive studies and various drugs have been used in an attempt to improve wound healing. There are conflicting data regarding the effects of L-arginine, the substrate of nitric oxide, on wound healing. We examined the 1-week rate of cutaneous wound healing and collagen deposition in three groups of rats who received a (1) L-arginine (2% in drinking water)-supplemented diet from three days before until the seventh day following injury (Group 1), (2) L-arginine-supplemented diet for three days before injury (Group 2), and (3) a standard diet without L-arginine supplementation (Group 3). The wound length and width were measured each day and then the open wound area and cumulative percentage of open wound area reduction were calculated. Wound biopsy samples were examined with Trichrome-Masson stain in a subgroup of animals. Results showed that Group 1 rats had a significantly lower cumulative percentage of open wound area reduction on day 7 compared to other two groups (Mann-Whitney U test, P < 0.05). Relatively higher degrees of wound collagen deposit (day 7) were noted in groups 2 and 3. It may be concluded that L-arginine (2% in water) administered three days before until the seventh day following skin wound induction may diminish the rate of skin wound healing and collagen deposition.

  3. Influence of L-arginine during bovine in vitro fertilization.

    PubMed

    Silva, Thiago Velasco Guimarães; da Silva, Bruno Baraúna; de Sá, André Luiz Alves; da Costa, Nathalia Nogueira; Sampaio, Rafael Vilar; Cordeiro, Marcela da Silva; Santana, Priscila Di Paula Bessa; Adona, Paulo Roberto; Santos, Simone do Socorro Damasceno; Miranda, Moysés dos Santos; Ohashi, Otávio Mitio

    2014-12-01

    The objective of this work was to evaluate the effect of using L-arginine during in vitro fertilization (IVF) on in vitro embryonic development using Bos taurus and Bos indicus semen. Effect of different concentrations (0, 1, 10 and 50 mM) of L-arginine, added to the IVF medium, was evaluated on the fertilization rate at 18 h post-fertilization (hpf), NO3(-)/NO2(-) production during IVF by the Griess colorimetric method (30 hpf), cleavage and blastocyst rates (on Day 2 and Day 7 of culture, respectively) and total blastocyst cell number (Day 7 of culture). The results reveal that the addition of 50 mM L-arginine to IVF medium, with either Bos taurus or Bos indicus spermatozoa, decreased the cleavage rate and blastocyst rate compared to the control group. Other concentrations did not affect embryo production. However, 1 mM L-arginine with Bos indicus semen increased the proportion of hatched blastocysts. These results indicate that high L-arginine concentrations may exhibit toxic effects on bovine gametes during in vitro fertilization.

  4. Long-term effects of oral vitamin C supplementation on the endothelial dysfunction in the iris microvessels of diabetic rats.

    PubMed

    Jariyapongskul, Amporn; Rungjaroen, Tippawan; Kasetsuwan, Ngamjit; Patumraj, Suthiluk; Seki, Junji; Niimi, Hideyukii

    2007-07-01

    The current study was aimed to investigate effects of long-term supplementation of vitamin C on the iris microcirculation in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar-Furth rats by intravenous injection of STZ (55 mg/kg b.w.). The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and STZ rats supplemented with vitamin C (STZ-vitC). For supplementation of vitamin C, ascorbic acid (1 g/l) was added into the drinking water. The experiments were performed at different periods (8, 12, 24 and 36 weeks) after injection of STZ. Blood glucose, tissue lipid peroxidation and plasma vitamin C were measured. To examine the endothelial function, leukocyte adhesion to the venular endothelium was evaluated in the iris post-capillaries by means of counting the number of leukocytes labeled with rhodamine 6G. Blood flow perfusion in the iris was monitored using a laser Doppler flow meter. In the STZ rats, hyperglycemia was induced with an increase in HbA(1c) and lipid peroxidation but with a decrease in the plasma vitamin C level which improved by vitamin C supplementation. The number of adherent leukocytes increased significantly, associated with reduction in the iris blood flow perfusion, at 8, 12, 24 and 36 weeks after injection of STZ. In the STZ-vitC rats, the iris blood flow perfusion was significantly increased in comparison with the STZ rats, while the leukocyte adhesion was decreased at 24 and 36 weeks. The statistical analysis shows that the leukocyte adhesion decreased with increase in the iris blood flow perfusion in STZ and STZ-vitC rats. In conclusion, vitamin supplementation suppressed leukocyte adhesion and thus endothelial dysfunction, associated with increase in iris blood flow perfusion in diabetes. The antioxidant vitamin C may be a therapeutic agent for preventing diabetic retinopathy.

  5. Disappearance of a uterine arteriovenous malformation following long-term administration of oral norgestrel/ethinyl estradiol.

    PubMed

    Oride, Aki; Kanasaki, Haruhiko; Miyazaki, Kohji

    2014-06-01

    Uterine arteriovenous malformation (AVM) can cause sudden massive hemorrhage. We report a case of uterine AVM following curettage in a patient treated conservatively with an intermediate-dose pill. An 18-year-old gravida 2 para 0 underwent curettage at 12 weeks of gestation and was examined for massive genital hemorrhage that occurred in postoperative month 4. Abundant blood flow in a mass within the uterine lumen was observed on color Doppler ultrasonography, and the patient was diagnosed with AVM. Six days after starting oral norgestrel/ethinyl estradiol, the hemorrhage ceased, and computed tomography on day 37 of administration showed disappearance of the abnormal vasculature. After 12 months, the patient's course remains favorable without relapse. Transarterial embolization for AVM can cause ovarian failure and subsequent placental malpositioning. Administration of oral norgestrel/ethinyl estradiol may be an alternative conservative treatment option for patients who wish to maintain fertility.

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

    PubMed Central

    Krannich, Alexander; Heine, Guido; Dölle, Sabine; Worm, Margitta

    2017-01-01

    Background and Objectives 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. Research design and methods 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(OH)D) concentrations were measured in all individuals at defined time points throughout the studies. Results The mean 25(OH)D 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(OH)D 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(OH)D serum concentrations after 28 days was comparable between both routes of administration (p = 0.264). Conclusions Oral and intramuscular cholecalciferol supplementation effectively increased serum 25(OH)D concentrations. PMID:28114352

  7. [Change in the incidence of diabetes mellitus in oral cancer patients based on a long-term comparative study].

    PubMed

    Végh, Dániel; Bányai, Dorottya; Ujpál, Márta

    2015-03-01

    Our research is focused on the incidence of diabetes mellitus and glucose metabolic disorders among oral cancer patients and the frequency of different oral localizations of cancer. Diabetes mellitus affects 7% of the Hungarian population. This study uses data spanning 14 years, with 2 datasets of 1998-1999 and 2012-2013, collected first hand by the authors. These datasets have led us to examine the blood glucose level in 267 patients with histologically confirmed malignant tumours in the oral cavity. Diabetes mellitus was found in 59 of them (22.1%), The blood glucose was elevated in 32 cases (12%). The most frequent tumor locations among the diabetic patients: labial, lingual and gingival tumors gingivae. Comparative epidemiological study demonstrates that in 2012-2013 dataset there was an increased observed percentage of people with diabetes mellitus [17.6% to 22.1%]. The percentage of patients with IFG (impaired fasting glucose) also increased from 9.8% to 12%. Overall the number of patients with glucose metabolic disorders climbed from 27.4% to 34.1%, (p > 0.05). Our intention of this introductory analysis is to emphasize the close connection of these two very important disease groups, and the wider spread of diabetes mellitus.

  8. 3-Dimensional liver volume assessment in patients with hepatitis B virus-related liver cirrhosis during long-term oral nucleos(t)ide analogues therapy

    PubMed Central

    Lee, Chang Hun; Kim, In Hee; Moon, Jin Chang; Seo, Seung Young; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae Ghon; Yang, Jae Do; Yu, Hee Chul

    2017-01-01

    AIM To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program. PMID:28127203

  9. Academic-practice partnerships to promote evidence-based practice in long-term care: oral hygiene care practices as an exemplar.

    PubMed

    McConnell, Eleanor Schildwachter; Lekan, Deborah; Hebert, Catherine; Leatherwood, Lisa

    2007-01-01

    Learning in practice disciplines suffers when gaps exist between classroom instruction and students' observations of routine clinical practices.(1) Academic institutions, therefore, have a strong interest in fostering the rapid and effective translation of evidence-based care techniques into routine practice. Long-term care (LTC) practice sites are particularly vulnerable to gaps between classroom teaching and how daily care is implemented, owing to the recent rapid advances in the scientific bases of care for frail older adults, the relative isolation of most LTC sites from academic settings,(2) and the relatively small number of registered nurses (RNs) available in LTC settings who can facilitate translation of research-based practices into care.(3) The aim of this project was to demonstrate the feasibility and value of an academic practice partnership to implement evidence-based approaches to solving resident care problems in LTC, as many scientifically proven practices hold promise for improving resident outcomes yet adoption is often slow.(4) We developed and implemented a clinical practice improvement process, based on diffusion of innovations theory and research,(5-8) to serve as a new model of academic-practice collaboration between a university school of nursing, LTC facility management and direct-care staff, as a means of developing high quality clinical sites for student rotations. The goal was to implement a sustainable evidence-based oral care program as an exemplar of how scientific evidence can be translated into LTC practice. This project focused on oral hygiene because the staff was dissatisfied with their existing resident oral care program, and an evidence-base for oral care in LTC existed that had not yet been incorporated into care routines. This article describes a systematic, replicable process for linking advanced practice registered nurse expertise with staff insights about care systems to reduce the gap between teaching and practice in

  10. Responses of dairy cattle to long-term and short-term supplementation with oral selenium and vitamin E

    SciTech Connect

    Stowe, H.D.; Thomas, J.W.; Johnson, T.; Marteniuk, J.V.; Morrow, D.A.; Ullrey, D.E. )

    1988-07-01

    In a two-lactation-gestation cycle experiment, 152 Holstein cows with low serum Se and vitamin E were fed total mixed rations and assigned at parturition to four groups (1, control; 2, 500 IU vitamin E/d; 3, 2 mg Se/d; 4, 500 IU vitamin E plus 2 mg Se/d). Supplements were not fed during dry periods. Serium Se and vitamin E were increased within 1 mo by oral supplements. Maximal mean serum Se in cycles 1 and 2 occurred in groups 3 and 4, respectively. Maximal mean serum vitamin E in cycle 1 and 2 occurred in groups 4 and 2, respectively. Selenium treatment of the dams increased Se in colostrum and in serum of presuckle calves. Vitamin E supplementation of dams did not affect vitamin E in serum of presuckled calves. Reproductive performance was not affected by supplement. In an 8-wk study, 24 lactating cows with low serum Se were assigned (6/group) to 0, 2.5, 5, and 10 mg supplemental Se/d. Maximal mean serum Se concentrations of 23, 56, 71, and 79 ng/ml were attained by wk 4 in the above respective groups. These data indicate that 2 to 2.5 mg supplemental Se/cow per d were inadequate for desirable serum Se concentrations and support recent changes in allowed Se supplementation for dairy cattle.

  11. Long-term effects of chronic oral Ritalin administration on cognitive and neural development in adolescent wistar kyoto rats.

    PubMed

    Pardey, Margery C; Kumar, Natasha N; Goodchild, Ann K; Clemens, Kelly J; Homewood, Judi; Cornish, Jennifer L

    2012-09-12

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed "normal" (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in "normal" WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  12. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    PubMed Central

    Pardey, Margery C.; Kumar, Natasha N.; Goodchild, Ann K.; Clemens, Kelly J.; Homewood, Judi; Cornish, Jennifer L.

    2012-01-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls. PMID:24961199

  13. Long-term Resolution of Blinding Polypoidal Choroidal Vasculopathy with Recurrent Bilateral Central Involvement by Low-dose Oral Eplerenone Treatment.

    PubMed

    Bialasiewicz, Alexander Arthur; Abdelhamid, Mahmoud; Shenoy, Radha; Barman, Manish

    2016-01-01

    A 55-year-old male presented with serous retinal detachment over 3 months in his right eye. His left eye was blind due to retinal pigment epithelium detachment since 1997 with atrophy of the neurosensory retina. Fluorescein angiography had previously shown bilateral polypoidal choroidal vasculopathy (PCV). Optical coherence tomography (OCT) confirmed PCV with central involvement. The patient underwent intravitreal injections of 6x Lucentis, 4x Avastin and one injection of aflibercept. PCV recurred from 1 to 4 months after each treatment. The patient had history of stroke, hypertension, and atrial fibrillation and was started on oral eplerenone 25 mg/day in October 2014, which resulted in a long-term ongoing complete retinal reattachment. OCT ganglion cell and inner plexiform layers showed full recovery of the fovea in the right eye and irreversible in the left eye. Low-dose eplerenone may resolve recalcitrant PCV with central involvement. The duration of treatment remains uncertain.

  14. Long-term Resolution of Blinding Polypoidal Choroidal Vasculopathy with Recurrent Bilateral Central Involvement by Low-dose Oral Eplerenone Treatment

    PubMed Central

    Bialasiewicz, Alexander Arthur; Abdelhamid, Mahmoud; Shenoy, Radha; Barman, Manish

    2016-01-01

    A 55-year-old male presented with serous retinal detachment over 3 months in his right eye. His left eye was blind due to retinal pigment epithelium detachment since 1997 with atrophy of the neurosensory retina. Fluorescein angiography had previously shown bilateral polypoidal choroidal vasculopathy (PCV). Optical coherence tomography (OCT) confirmed PCV with central involvement. The patient underwent intravitreal injections of 6x Lucentis, 4x Avastin and one injection of aflibercept. PCV recurred from 1 to 4 months after each treatment. The patient had history of stroke, hypertension, and atrial fibrillation and was started on oral eplerenone 25 mg/day in October 2014, which resulted in a long-term ongoing complete retinal reattachment. OCT ganglion cell and inner plexiform layers showed full recovery of the fovea in the right eye and irreversible in the left eye. Low-dose eplerenone may resolve recalcitrant PCV with central involvement. The duration of treatment remains uncertain. PMID:27162459

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

    PubMed Central

    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 < 0.001 vs. placebo). However, no significant differences in changes in peripheral nerve function or soluble inflammatory biomarkers were observed between the groups. CONCLUSIONS Our findings suggest that high-dose 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

  16. Long-Term Oral Nutrition Supplementation Improves Outcomes in Malnourished Patients With Chronic Kidney Disease on Hemodialysis

    PubMed Central

    Bal, Zeynep; Tutal, Emre; Uyar, Mehtap Erkmen; Acar, Nurhan Ozdemir

    2014-01-01

    Background: There is no consensus on the type, time of initiation, or duration of use of enteral nutrition in patients with chronic kidney disease (CKD). This study aimed to compare the effects of a renal-specific oral nutrition supplement (RS-ONS) and a standard recommended nutrition regime on biochemical and nutrition markers in malnourished patients with CKD on hemodialysis. Methods: Sixty-two malnourished patients with CKD, divided into experimental (RS-ONS; n = 32; mean [SD] age, 62.0 [11.3] years; 55.2% female) and control (CON; n = 30; mean [SD] age, 57.2 [12.3] years; 31% female) groups, were evaluated for anthropometric, biochemical, and inflammatory parameters. Results: Mean (SD) serum albumin levels were significantly increased in the RS-ONS group from 3.5 (0.3) g/dL at baseline to 3.7 (0.2) g/dL at 6 months (P = .028). Significantly fewer patients had serum albumin levels of <3.5 g/dL after month 6. Dry weight of patients significantly increased in the RS-ONS but decreased in the CON groups (P < .001 for each). Percent change from baseline revealed negative results for bioelectrical impedance analysis (P < .001) in the CON group. Malnutrition inflammation score at 6 months (P = .006) and erythropoietin (EPO) dose requirements were higher in the CON group (P = .012). Conclusions: Our findings indicate that consuming RS-ONS improves serum albumin and anthropometric measures, as well as reduces EPO dose, in patients with CKD. PMID:24436491

  17. Regulation of macrophage functions by L-arginine

    PubMed Central

    1989-01-01

    Sites of inflammation with prominent macrophage infiltration, such as wounds and certain tumors, are uniquely deficient in free arginine. The effects of arginine availability on macrophage physiology were investigated. When cultured in media containing less than 0.1 mM L- arginine, rat resident peritoneal macrophages exhibited enhanced spreading, tumor cytotoxicity, superoxide production, phagocytosis, and protein synthesis. Thus, arginine concentrations similar to those found in sites of inflammation can augment macrophage functions, while those found in plasma (approximately 0.1 mM) and in commonly used culture media (0.4 to 1.2 mM) are inhibitory. Culture in homoarginine, but not D-arginine, ornithine, citrulline, urea, histidine, or lysine also inhibited macrophage tumor cytotoxicity, indicating the specificity of the effect. In contrast to resident macrophages, the tumor cytotoxicity of peritoneal macrophages obtained after C. parvum injection was suppressed by culture in arginine-deficient media. However, L-arginine- deficient media enhanced all other activation-associated functions in C. parvum-elicited macrophages as in resident cells. Arginine-free wound fluid promoted resident macrophage tumoricidal activity when compared with rat serum, and again, the addition of L-arginine was inhibitory. The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation. PMID:2538541

  18. Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.

    PubMed Central

    Cooke, J P; Singer, A H; Tsao, P; Zera, P; Rowan, R A; Billingham, M E

    1992-01-01

    The purpose of this study was to determine if chronic administration of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF), normalizes endothelium-dependent relaxation and decreases atherosclerosis in hypercholesterolemic animals. Male rabbits were fed (a) normal rabbit chow; (b) 1% cholesterol diet; or (c) 1% cholesterol diet supplemented by 2.25% L-arginine HCl in drinking water. Arginine supplementation doubled plasma arginine levels without affecting serum cholesterol values. After 10 wk, the thoracic aorta was harvested for studies of vascular reactivity and histomorphometry. Endothelium-dependent relaxations (to acetylcholine and calcium ionophore A23187) were significantly impaired in thoracic aortae from animals fed a 1% cholesterol diet. By contrast, vessels from hypercholesterolemic animals receiving L-arginine supplementation exhibited significantly improved endothelium-dependent relaxations. Responses to norepinephrine or nitroglycerin were not affected by either dietary intervention. Histomorphometric analysis revealed a reduction in lesion surface area and intimal thickness in thoracic aortae from arginine-supplemented animals compared to those from untreated hypercholesterolemic rabbits. This is the first study to demonstrate that supplementation of dietary L-arginine, the EDRF precursor, improves endothelium-dependent vasorelaxation. More importantly, we have shown that this improvement in EDRF activity is associated with a reduction in atherogenesis. PMID:1522225

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

    SciTech Connect

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

    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 the cell

  20. Long-term effects of palatal plate therapy on oral motor function in children with Down syndrome evaluated by video registration.

    PubMed

    Carlstedt, K; Henningsson, G; McAllister, A; Dahllöf, G

    2001-04-01

    Oral motor function was evaluated after 4 years of palatal plate therapy in nine children with Down syndrome (DS); 11 children with DS constituted the control group. During the treatment period all children had orofacial physiotherapy with their speech pathologist. An extraoral examination was performed, as was a video registration of the face. Nine different variables showing positions of the lips, tongue, and facial expression were examined. Children in the palatal plate group (n = 9) had significantly more rounding lips during speech (P< 0.05) than children in the control group (n = 11). The active variables describing normal muscle tension were diagnosed to constitute 81.0% +/- 11.0% of the registered video time in the palatal plate group, compared with 68.2% +/- 22.5% in the control group. Statistically significant differences were found between the groups in the summary variables describing an inactive open mouth and inactive tongue protrusion (P< 0.01). The results indicate that palatal plate therapy has a long-term effect on oral motor function.

  1. Long-term quality of life after intensified multi-modality treatment of oral cancer including intra-arterial induction chemotherapy and adjuvant chemoradiation

    PubMed Central

    Kovács, Adorján F.; Stefenelli, Ulrich; Thorn, Gerrit

    2015-01-01

    Background: Quality of life (QoL) studies are well established when accompanying trials in head and neck cancer, but studies on long-term survivors are rare. Aims: The aim was to evaluate long-term follow-up patients treated with an intensified multi-modality therapy. Setting and Design: Cross-sectional study, tertiary care center. Patients and Methods: A total of 135 oral/oropharyngeal cancer survivors having been treated with an effective four modality treatment (intra-arterial induction chemotherapy, radical surgery, adjuvant radiation, concurrent systemic chemotherapy) filled European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and HN35 questionnaires. Mean distance to treatment was 6.1 (1.3–16.6) years. Results were compared with a reference patient population (EORTC reference manual). In-study group comparison was also carried out. Statistical Analysis: One-sample t-test, Mann–Whitney-test, Kruskal–Wallis analysis. Results: QoL scores of both populations were well comparable. Global health status, cognitive and social functioning, fatigue, social eating, status of teeth, mouth opening and dryness, and sticky saliva were significantly worse in the study population; pain and need for pain killers, cough, need for nutritional support, problems with weight loss and gain were judged to be significantly less. Patients 1-year posttreatment had generally worse scores as compared to patients with two or more years distance to treatment. Complex reconstructive measures and adjuvant (chemo) radiation were main reasons for significant impairment of QoL. Conclusion Subjective disease status of patients following a maximized multi-modality treatment showed an expectable high degree of limitations, but was generally comparable to a reference group treated less intensively, suggesting that the administration of an intensified multi-modality treatment is feasible in terms of QoL/effectivity ratio. PMID:26389030

  2. Long-term effects of oral tea polyphenols and Lactobacillus brevis M8 on biochemical parameters, digestive enzymes, and cytokines expression in broilers.

    PubMed

    Li, Hua-li; Li, Zong-jun; Wei, Zhong-shan; Liu, Ting; Zou, Xiao-zuo; Liao, Yong; Luo, Yu

    2015-12-01

    This study investigates the long-term effects of oral tea polyphenols (TPs) and Lactobacillus brevis M8 (LB) on biochemical parameters, digestive enzymes, and cytokines expression in broilers. In experiment 1, 240 broiler chickens were selected to investigate the effects of 0.06 g/kg body weight (BW) TP and 1.0 ml/kg BW LB on broilers; in experiment 2, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of TP (0.03, 0.06, and 0.09 g/kg BW) combined with 1.0 ml/kg BW LB on broilers; in experiment 3, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of LB (0.5, 1.0, and 1.5 ml/kg BW) combined with 0.06 g/kg BW TP on broilers. The results showed that TP and LB affected serum biochemical parameters, and TP reduced serum cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) abundances in a dosage-dependent manner (P<0.05) on Day 84. Meanwhile, broilers fed a diet supplemented with TP or LB had a lower intestinal lipase activity on Day 84 compared with the control group (P<0.05). Middle and high dosages of TP increased pancreatic lipase and proventriculus pepsin activities (P<0.05). Also middle and high dosages of LB significantly enhanced pancreatic lipase activity (P<0.05), while high LB supplementation inhibited intestinal trypsase (P<0.05) on Day 84. Furthermore, both TP and LB reduced intestinal cytokine expression and nuclear factor-κ B (NF-κB) mRNA level on Days 56 and 84. In conclusion, long-term treatment of TP and LB improved lipid metabolism and digestive enzymes activities, and affected intestinal inflammatory status, which may be associated with the NF-κB signal.

  3. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular

  4. Effect of oral beta-blocker on short and long-term mortality in patients with acute respiratory failure: results from the BASEL-II-ICU study

    PubMed Central

    2010-01-01

    Introduction Acute respiratory failure (ARF) is responsible for about one-third of intensive care unit (ICU) admissions and is associated with adverse outcomes. Predictors of short- and long-term outcomes in unselected ICU-patients with ARF are ill-defined. The purpose of this analysis was to determine predictors of in-hospital and one-year mortality and assess the effects of oral beta-blockers in unselected ICU patients with ARF included in the BASEL-II-ICU study. Methods The BASEL II-ICU study was a prospective, multicenter, randomized, single-blinded, controlled trial of 314 (mean age 70 (62 to 79) years) ICU patients with ARF evaluating impact of a B-type natriuretic peptide- (BNP) guided management strategy on short-term outcomes. Results In-hospital mortality was 16% (51 patients) and one-year mortality 41% (128 patients). Multivariate analysis assessed that oral beta-blockers at admission were associated with a lower risk of both in-hospital (HR 0.33 (0.14 to 0.74) P = 0.007) and one-year mortality (HR 0.29 (0.16 to 0.51) P = 0.0003). Kaplan-Meier analysis confirmed the lower mortality in ARF patients when admitted with oral beta-blocker and further shows that the beneficial effect of oral beta-blockers at admission holds true in the two subgroups of patients with ARF related to cardiac or non-cardiac causes. Kaplan-Meier analysis also shows that administration of oral beta-blockers before hospital discharge gives striking additional beneficial effects on one-year mortality. Conclusions Established beta-blocker therapy appears to be associated with a reduced mortality in ICU patients with acute respiratory failure. Cessation of established therapy appears to be hazardous. Initiation of therapy prior to discharge appears to confer benefit. This finding was seen regardless of the cardiac or non-cardiac etiology of respiratory failure. Trial registration clinicalTrials.gov Identifier: NCT00130559 PMID:21047406

  5. Effects of NG-nitro-L-arginine and L-arginine on regional cerebral blood flow in the cat.

    PubMed Central

    Kovách, A G; Szabó, C; Benyó, Z; Csáki, C; Greenberg, J H; Reivich, M

    1992-01-01

    1. We studied the effects of NG-nitro-L-arginine (NOLA), a potent inhibitor of the L-arginine-nitric oxide pathway, and L-arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg-1 bolus followed by 1 mg kg-1 min-1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L-arginine (30 mg kg-1 bolus followed by 10 mg kg-1 min-1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA-induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto-occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline-induced contractions and N-ethoxycarbonyl-3-morpholino-sydnonimine (SIN-1)-induced relaxations and markedly attenuated acetylcholine- and ATP-induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L-arginine in a regionally heterogenous way and that exogenous L-arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the

  6. Production of l-Arginine by Arginine Hydroxamate-Resistant Mutants of Bacillus subtilis

    PubMed Central

    Kisumi, Masahiko; Kato, Jyoji; Sugiura, Masaki; Chibata, Ichiro

    1971-01-01

    l-Arginine hydroxamate inhibited the growth of various bacteria, and the inhibition was readily reversed by arginine. l-Arginine hydroxamate (10−3m) completely inhibited the growth of Bacillus subtilis. This inhibitory effect was prevented by 2.5 × 10−4ml-arginine, which was the most effective of all the natural amino acids in reversing the inhibition. l-Arginine hydroxamate-resistant mutants of Bacillus subtilis were isolated and found to excrete l-arginine in relatively high yields. One of the mutants, strain AHr-5, produced 4.5 mg of l-arginine per ml in shaken culture in 3 days. PMID:5002904

  7. Long-term effects of oral tea polyphenols and Lactobacillus brevis M8 on biochemical parameters, digestive enzymes, and cytokines expression in broilers

    PubMed Central

    Li, Hua-li; Li, Zong-jun; Wei, Zhong-shan; Liu, Ting; Zou, Xiao-zuo; Liao, Yong; Luo, Yu

    2015-01-01

    This study investigates the long-term effects of oral tea polyphenols (TPs) and Lactobacillus brevis M8 (LB) on biochemical parameters, digestive enzymes, and cytokines expression in broilers. In experiment 1, 240 broiler chickens were selected to investigate the effects of 0.06 g/kg body weight (BW) TP and 1.0 ml/kg BW LB on broilers; in experiment 2, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of TP (0.03, 0.06, and 0.09 g/kg BW) combined with 1.0 ml/kg BW LB on broilers; in experiment 3, 180 broiler chickens were assigned randomly to three groups to investigate the effects of different dosages of LB (0.5, 1.0, and 1.5 ml/kg BW) combined with 0.06 g/kg BW TP on broilers. The results showed that TP and LB affected serum biochemical parameters, and TP reduced serum cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) abundances in a dosage-dependent manner (P<0.05) on Day 84. Meanwhile, broilers fed a diet supplemented with TP or LB had a lower intestinal lipase activity on Day 84 compared with the control group (P<0.05). Middle and high dosages of TP increased pancreatic lipase and proventriculus pepsin activities (P<0.05). Also middle and high dosages of LB significantly enhanced pancreatic lipase activity (P<0.05), while high LB supplementation inhibited intestinal trypsase (P<0.05) on Day 84. Furthermore, both TP and LB reduced intestinal cytokine expression and nuclear factor-κ B (NF-κB) mRNA level on Days 56 and 84. In conclusion, long-term treatment of TP and LB improved lipid metabolism and digestive enzymes activities, and affected intestinal inflammatory status, which may be associated with the NF-κB signal. PMID:26642185

  8. L-arginine increases nitric oxide and attenuates pressor and heart rate responses to change in posture in sickle cell anemia subjects.

    PubMed

    Ogungbemi, S I; Anigbogu, C N; Kehinde, M O; Jaja, S I

    2013-06-30

    Pressor and heart rate changes following change in posture without or with L-arginine supplementation (1g/day for 6 weeks) were studied in 28 sickle cell anemia (SCA) and 32 non-sickle cell anemia (NSCA) subjects. Change in posture increased HR (p<0.01), RPP (p<0.05) in both groups of subjects, MABP (p<0.05) in SCAS but reduced MABP (p<0.01) in NSCAS and PP (p<0.01) in SCAS. L-Arginine supplementation increased plasma L-Arginine concentration ([R]) in both groups of subjects (p<0.001 in each group) and serum nitric oxide metabolites concentration ([NOx]) (p<0.01 in each group). Change (Δ) [R] correlated positively with Δ [NOx] in both groups (+ 0.7 in each group). L-Arginine supplementation caused greater reduction of MABP (p<0.001) in NSCAS than in SCAS. However, reduction in HR was greater (p<0.001) in SCAS than in NSCAS. After supplementation, MABP and PP responses to change in posture were attenuated in the two groups. However, while HR and RPP responses in SCAS were attenuated, the same responses were enhanced in NSCAS by change in posture after supplementation. In conclusion, study shows that oral, low dose, chronic supplementation with L-arginine increased NO availability and attenuated pressor and heart rate responses to change in posture in sickle cell anemia subjects.

  9. Oral health-related quality of life and depression/anxiety in long-term recurrence-free patients after treatment for advanced oral squamous cell cancer.

    PubMed

    Hassel, Alexander J; Danner, Daniel; Freier, Kolja; Hofele, Christof; Becker-Bikowski, Kirsten; Engel, Michael

    2012-06-01

    This report focuses on the association between oral health-related quality of life (OHRQoL) and depression/anxiety of a homogeneous group of cancer patients who were recurrence-free for 8 years after treatment for advanced oral squamous cell. Participants were 24 patients (mean age 55 years, 75% men) treated with neoadjuvant concurrent radiochemotherapy followed by surgery with a mean recurrence-free period of 95 months (from 39 to 164 months). The OHRQoL (OHIP) and the anxiety/depression (HADS) were assessed twice (1 year between t1 and t2). OHRQoL was impaired in this group (mean OHIP score 65 units). In cross-lagged correlation analysis, the correlation between OHRQoL to t1 and depression to t2 was significant and greater than the non-significant correlation for depression to t1 and OHRQoL to t2 indicating that OHRQoL predicts depression better than vice versa. However, the difference in the correlation coefficients was not significant (ZPF-test). The same was true for OHRQoL and anxiety. The OHRQoL measured with the OHIP was impaired in comparison to the normal population. In the limitations of the study design and bearing the small sample size in mind, the results give evidence that OHRQoL predicts psychological outcomes, namely depression and anxiety, better than vice versa.

  10. Improvement of the ammonia assimilation for enhancing L-arginine production of Corynebacterium crenatum.

    PubMed

    Guo, Jing; Man, Zaiwei; Rao, Zhiming; Xu, Meijuan; Yang, Taowei; Zhang, Xian; Xu, Zhenghong

    2017-03-01

    There are four nitrogen atoms in L-arginine molecule and the nitrogen content is 32.1%. By now, metabolic engineering for L-arginine production strain improvement was focused on carbon flux optimization. In previous work, we obtained an L-arginine-producing Corynebacterium crenatum SDNN403 (ARG) through screening and mutation breeding. In this paper, a strain engineering strategy focusing on nitrogen supply and ammonium assimilation for L-arginine production was performed. Firstly, the effects of nitrogen atom donor (L-glutamate, L-glutamine and L-aspartate) addition on L-arginine production of ARG were studied, and the addition of L-glutamine and L-aspartate was beneficial for L-arginine production. Then, the glutamine synthetase gene glnA and aspartase gene aspA from E. coli were overexpressed in ARG for increasing the L-glutamine and L-aspartate synthesis, and the L-arginine production was effectively increased. In addition, the L-glutamate supply re-emerged as a limiting factor for L-arginine biosynthesis. Finally, the glutamate dehydrogenase gene gdh was co-overexpressed for further enhancement of L-arginine production. The final strain could produce 53.2 g l(-1) of L-arginine, which was increased by 41.5% compared to ARG in fed-batch fermentation.

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

    NASA Astrophysics Data System (ADS)

    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.

  12. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure.

    PubMed

    Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Konjevoda, P; Perović, D; Jurina, L; Separović, J; Hanzevacki, M; Artuković, B; Bratulić, M; Tisljar, M; Gjurasin, M; Miklić, P; Stancić-Rokotov, D; Slobodnjak, Z; Jelovac, N; Marović, A

    1997-07-30

    The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L-arginine

  13. Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans.

    PubMed

    Mittermayer, Friedrich; Namiranian, Khodadad; Pleiner, Johannes; Schaller, Georg; Wolzt, Michael

    2004-06-01

    Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L-arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [95% CI (confidence interval): 56, 88] at baseline to 48 micromol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L-arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L-Arginine, ADMA, SDMA and the L-arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function.

  14. Systems pathway engineering of Corynebacterium crenatum for improved L-arginine production

    PubMed Central

    Man, Zaiwei; Xu, Meijuan; Rao, Zhiming; Guo, Jing; Yang, Taowei; Zhang, Xian; Xu, Zhenghong

    2016-01-01

    L-arginine is an important amino acid in food and pharmaceutical industries. Until now, the main production method of L-arginine in China is the highly polluting keratin acid hydrolysis. The industrial level L-arginine production by microbial fermentation has become an important task. In previous work, we obtained a new L-arginine producing Corynebacterium crenatum (subspecies of Corynebacterium glutamicum) through screening and mutation breeding. In this work, we performed systems pathway engineering of C. crenatum for improved L-arginine production, involving amplification of L-arginine biosynthetic pathway flux by removal of feedback inhibition and overexpression of arginine operon; optimization of NADPH supply by modulation of metabolic flux distribution between glycolysis and pentose phosphate pathway; increasing glucose consumption by strengthening the preexisting glucose transporter and exploitation of new glucose uptake system; channeling excess carbon flux from glycolysis into tricarboxylic acid cycle to alleviate the glucose overflow metabolism; redistribution of carbon flux at α-ketoglutarate metabolic node to channel more flux into L-arginine biosynthetic pathway; minimization of carbon and cofactor loss by attenuation of byproducts formation. The final strain could produce 87.3 g L−1 L-arginine with yield up to 0.431 g L-arginine g−1 glucose in fed-batch fermentation. PMID:27338253

  15. Dietary L-arginine decreases myointimal cell proliferation and vascular monocyte accumulation in cholesterol-fed rabbits.

    PubMed

    Böger, R H; Bode-Böger, S M; Kienke, S; Stan, A C; Nafe, R; Frölich, J C

    1998-01-01

    L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to enhance endothelial function and to reduce the progression of atherosclerosis in cholesterol-fed rabbits. In the present study, we investigated whether myointimal cell proliferation is enhanced in hypercholesterolaemic rabbit aorta and whether chronic treatment of the rabbits with L-arginine or with the NO synthase inhibitor L-NAME influences this proliferative response and vascular monocyte accumulation. Rabbits were fed 1% cholesterol or normal rabbit chow for 12 weeks. Subgroups of cholesterol-fed rabbits were treated with oral L-arginine (2.25%) or L-NAME (3 mg/dl) in drinking water. Myointimal cell proliferation was quantified in aortic segments by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation into nuclear DNA; vascular monocyte accumulation was assessed by immunohistochemistry using a monoclonal anti-macrophage/monocyte antibody (RAM-11). Plasma levels of L-arginine and the endogenous NO synthase inhibitor, ADMA, were quantified by high-performance liquid chromatography (HPLC). Cholesterol feeding increased the aortic intima/media (I/M) ratio, which was not measurable in the control group, to 1.9 +/- 0.3. This was paralleled by enhanced cell proliferation (cholesterol, 2.4 +/- 0.2%; P < 0.05; control, 0.02 +/- 0.001% BrdU-positive cells per 72 h) and vascular monocyte accumulation. Double immunostaining for BrdU and alpha-actin showed that about two thirds of the proliferating cells were smooth muscle cells. ADMA levels increased from 0.8 +/- 0.1 micromol/l to 2.2 +/- 0.2 micromol/l in cholesterol-fed rabbits, but were unchanged by L-arginine or L-NAME treatment. Myointimal proliferation and intima/media ratios were correlated with ADMA plasma levels. Dietary L-arginine reduced monocyte accumulation by 85 +/- 2% (P < 0.05 vs cholesterol), myointimal cell proliferation (1.8 +/- 0.3% per 72 h; P < 0.05) and intimal thickening (I/M ratio: 0.7 +/- 0.2), whereas

  16. Characterization of casein and poly-L-arginine multilayer films.

    PubMed

    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. α- and β-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). (PLArg/casein) films deposited in 0.15M NaCl exhibit fast (exponential-like) growth of the film thickness with the number of layers. The resulting films were c.a. 10 times thicker than obtained for poly-L-arginine and natural polyanions. We investigated the effect of the type of casein used for the film formation, finding that films with α-casein were slightly thicker than ones with β-casein. The effect of polyethylene imine anchoring layer on the thickness and mass of adsorbed films was similar as for linear polyelectrolyte pairs. Thickness of "wet" films was c.a. two times larger than measured after drying that suggests their large hydration. 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. Films remain stable in the neutral and weakly basic conditions that includes HEPES buffer, which is widely used in cell culture and biomedical experiments. At the conditions of high ionic strength films swell but their swelling is reversible. Films containing caseins as polyanion appear to be more elastic and the same time more viscous than one formed with polyelectrolyte pairs. XPS elemental analysis confirmed binding of calcium ions by the casein embedded in the multilayers.

  17. Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives.

    PubMed

    Heresztyn, Tamila; Worthley, Matthew I; Horowitz, John D

    2004-06-15

    A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients.

  18. Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats

    PubMed Central

    Başhan, İbrahim; Başhan, Perihan; Seçilmiş, Mehmet Ata; Şingirik, Ergin

    2014-01-01

    Introduction: L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats. Materials and Methods: Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique. Results: Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination. Conclusion: Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in

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

    PubMed Central

    Schriek, Sarah; Rückert, Christian; Staiger, Dorothee; Pistorius, Elfriede K; Michel, Klaus-Peter

    2007-01-01

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

  20. L-arginine regulates neuronal nitric oxide synthase production of superoxide and hydrogen peroxide.

    PubMed

    Tsai, Pei; Weaver, John; Cao, Guan Liang; Pou, Sovitj; Roman, Linda J; Starkov, Anatoly A; Rosen, Gerald M

    2005-03-15

    Tetrahydrobiopterin (H(4)B) in the absence of L-arginine has been shown to be an important factor in promoting the direct formation of hydrogen peroxide (H(2)O(2)) at the expense of superoxide (O(2)(*-)) by neuronal nitric oxide synthase (NOS1) [Rosen GM, Tsai P, Weaver J, Porasuphatana S, Roman LJ, Starkov AA, et al. Role of tetrahydrobiopterin in the regulation of neuronal nitric-oxide synthase-generated superoxide. J Biol Chem 2002;277:40275-80]. Based on these findings, it is hypothesized that L-arginine also shifts the equilibrium between O(2)(*-) and H(2)O(2). Experiments were designed to test this theory. As the concentration of L-arginine and N(omega)-hydroxyl-L-arginine increases, the rate of NADPH consumption for H(4)B-bound NOS1 decreased resulting in lower rates of both O(2)(*-) and H(2)O(2) generation, while increasing the rate of nitric oxide (*NO) production. At saturating concentrations of L-arginine or N(omega)-hydroxyl-L-arginine (50microM), NOS1 still produced O(2)(*-) and H(2)O(2). Both L-arginine and N(omega)-hydroxyl-L-arginine have greater impact on the rate of generation of O(2)(*-) than on H(2)O(2).

  1. Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

    PubMed

    Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

    2017-04-01

    While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in

  2. Supplementation with l-arginine stabilizes plasma arginine and nitric oxide metabolites, suppresses elevated liver enzymes and peroxidation in sickle cell anaemia.

    PubMed

    Jaja, S I; Ogungbemi, S O; Kehinde, M O; Anigbogu, C N

    2016-06-01

    The effect of l-arginine on liver function in SCD has received little or no attention. The effect of a chronic, oral, low-dose supplementation with l-arginine (1gm/day for 6 weeks) on some liver enzymes, lipid peroxidation and nitric oxide metabolites was studied in 20 normal (non-sickle cell anaemia; NSCA) subjects and 20 sickle cell anaemia (SCA) subjects. Ten milliliters of blood was withdrawn from an ante-cubital vein for the estimation of plasma arginine concentration ([R]), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST) and alkaline phosphatase (ALP), plasma total bilirubin concentration [TB], malondialdehyde concentration [MDA] and nitric oxide metabolites concentration [NOx]. Before supplementation, ALT, AST, ALP (p<0.05 respectively) and TB (p<0.001) were higher in SCA subjects than in NSCA subjects. [R] and [NOx] were higher in NSCA subjects (p<0.001 and p<0.05 respectively). Supplementation caused greater percent increases in [R], and [NOX] in SCA than in NSCA subjects (p<0.001 in each case). l-Arginine caused greater percent reductions in ALT and AST in SCA subjects but greater percent reduction in ALP in NSCA subjects (p<0.001 in each case). Changes in [MDA] and [TB] in the two groups were similar. Study shows that chronic, oral, low-dose supplementation with l-arginine improved liver function, oxidative stress, plasma arginine concentration and nitric oxide metabolites levels in NSCA and SCA subjects. Responses in SCA subjects to l-arginine were more sensitive than in NSCA subjects.

  3. Vasodilator effects of L-arginine are stereospecific and augmented by insulin in humans.

    PubMed

    Dallinger, Susanne; Sieder, Anna; Strametz, Jeanette; Bayerle-Eder, Michaela; Wolzt, Michael; Schmetterer, Leopold

    2003-06-01

    The amino acid l-arginine, the precursor of nitric oxide (NO) synthesis, induces vasodilation in vivo, but the mechanism behind this effect is unclear. There is, however, some evidence to assume that the l-arginine membrane transport capacity is dependent on insulin plasma levels. We hypothesized that vasodilator effects of l-arginine may be dependent on insulin plasma levels. Accordingly, we performed two randomized, double-blind crossover studies in healthy male subjects. In protocol 1 (n = 15), subjects received an infusion of insulin (6 mU x kg(-1) x min(-1) for 120 min) or placebo and, during the last 30 min, l-arginine or d-arginine (1 g/min for 30 min) x In protocol 2 (n = 8), subjects received l-arginine in stepwise increasing doses in the presence (1.5 mU x kg(-1) x min(-1)) or absence of insulin. Renal plasma flow and glomerular filtration rate were assessed by the para-aminohippurate and inulin plasma clearance methods, respectively. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation, and mean flow velocity in the ophthalmic artery was measured with Doppler sonography. l-arginine, but not d-arginine, significantly increased renal and ocular hemodynamic parameters. Coinfusion of l-arginine with insulin caused a dose-dependent leftward shift of the vasodilator effect of l-arginine. This stereospecific renal and ocular vasodilator potency of l-arginine is enhanced by insulin, which may result from facilitated l-arginine membrane transport, enhanced intracellular NO formation, or increased NO bioavailability.

  4. Protection against cognitive deficits and markers of neurodegeneration by long-term oral administration of melatonin in a transgenic model of Alzheimer disease.

    PubMed

    Olcese, James M; Cao, Chuanhai; Mori, Takashi; Mamcarz, Malgorzata B; Maxwell, Anne; Runfeldt, Melissa J; Wang, Li; Zhang, Chi; Lin, Xiaoyang; Zhang, Guixin; Arendash, Gary W

    2009-08-01

    The neurohormone melatonin has been reported to exert anti-beta-amyloid aggregation, antioxidant, and anti-inflammatory actions in various in vitro and animal models. To comprehensively determine the potential for long-term melatonin treatment to protect Alzheimer's transgenic mice against cognitive impairment and development of beta-amyloid (Abeta) neuropathology, we administered melatonin (100 mg/L drinking water) to APP + PS1 double transgenic (Tg) mice from 2-2.5 months of age to their killing at age 7.5 months. A comprehensive behavioral battery administered during the final 6 weeks of treatment revealed that Tg mice given melatonin were protected from cognitive impairment in a variety of tasks of working memory, spatial reference learning/memory, and basic mnemonic function; Tg control mice remained impaired in all of these cognitive tasks/domains. Immunoreactive Abeta deposition was significantly reduced in hippocampus (43%) and entorhinal cortex (37%) of melatonin-treated Tg mice. Although soluble and oligomeric forms of Abeta1-40 and 1-42 were unchanged in the hippocampus and cortex of the same melatonin-treated Tg mice, their plasma Abeta levels were elevated. These Abeta results, together with our concurrent demonstration that melatonin suppresses Abeta aggregation in brain homogenates, are consistent with a melatonin-facilitated removal of Abeta from the brain. Inflammatory cytokines such as tumor necrosis factor (TNF)-alpha were decreased in hippocampus (but not plasma) of Tg+ melatonin mice. Finally, the cortical mRNA expression of three antioxidant enzymes (SOD-1, glutathione peroxidase, and catalase) was significantly reduced to non-Tg levels by long-term melatonin treatment in Tg mice. Thus, melatonin's cognitive benefits could involve its anti-Abeta aggregation, anti-inflammatory, and/or antioxidant properties. Our findings provide support for long-term melatonin therapy as a primary or complementary strategy for abating the progression of

  5. High Oral Human Papillomavirus Type 16 Load Predicts Long-term Persistence in Individuals With or at Risk for HIV Infection

    PubMed Central

    Beachler, Daniel C.; Guo, Yingshi; Xiao, Wiehong; Burk, Robert D.; Minkoff, Howard; Strickler, Howard D.; Cranston, Ross D.; Wiley, Dorothy J.; Jacobson, Lisa P.; Weber, Kathleen M.; Margolick, Joseph B.; Sugar, Elizabeth A.; Reddy, Susheel; Gillison, Maura L.; D'Souza, Gypsyamber

    2015-01-01

    The association between oral human papillomavirus 16 (HPV16) DNA load and infection clearance was evaluated among 88 individuals with oral HPV16 infection who were identified within a prospective cohort of 1470 HIV-infected and uninfected individuals. Oral rinse specimens were collected semiannually for up to 5 years. The oral HPV16 load at the time of the first positive test result was significantly associated with the time to clearance of infection (continuous P trends <.01). Notably, clearance rates by 24 months were 41% and 94% in the highest and lowest HPV16 load tertiles (P = .03), respectively. High oral HPV16 load warrants consideration as a biomarker for infection persistence, the presumed precursor of HPV16-associated oropharyngeal cancer. PMID:25954049

  6. High Oral Human Papillomavirus Type 16 Load Predicts Long-term Persistence in Individuals With or at Risk for HIV Infection.

    PubMed

    Beachler, Daniel C; Guo, Yingshi; Xiao, Wiehong; Burk, Robert D; Minkoff, Howard; Strickler, Howard D; Cranston, Ross D; Wiley, Dorothy J; Jacobson, Lisa P; Weber, Kathleen M; Margolick, Joseph B; Sugar, Elizabeth A; Reddy, Susheel; Gillison, Maura L; D'Souza, Gypsyamber

    2015-11-15

    The association between oral human papillomavirus 16 (HPV16) DNA load and infection clearance was evaluated among 88 individuals with oral HPV16 infection who were identified within a prospective cohort of 1470 HIV-infected and uninfected individuals. Oral rinse specimens were collected semiannually for up to 5 years. The oral HPV16 load at the time of the first positive test result was significantly associated with the time to clearance of infection (continuous P trends <.01). Notably, clearance rates by 24 months were 41% and 94% in the highest and lowest HPV16 load tertiles (P = .03), respectively. High oral HPV16 load warrants consideration as a biomarker for infection persistence, the presumed precursor of HPV16-associated oropharyngeal cancer.

  7. Effect of nitrate and L-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats.

    PubMed

    Ghasemi, Asghar; Mehrazin, Fatemeh; Zahediasl, Saleh

    2013-12-01

    Reduced nitric oxide availability and a heterogeneous pattern of nitric oxide synthase activity in some tissues have been reported in hypothyroidism. This study aimed at determining the effects of oral nitrate and L-arginine administration on serum, heart, and aorta nitric oxide metabolite concentrations in fetal hypothyroid rats. In an experimental study, pregnant Wistar rats were administrated tap water or 0.02 % of 6-propyl-2-thiouracil in drinking water during pregnancy and their male pups were followed (n = 8/group). In adult progeny, serum, heart, and aorta nitric oxide metabolite concentrations were measured by the Griess method after 1-week administration of sodium nitrate (500 mg/L) or L-arginine (2 %) in drinking water. Serum thyroid hormone and thyroid-stimulating hormone levels were also measured. Compared to controls, fetal hypothyroid progeny had significantly lower nitric oxide metabolite concentrations in heart (0.32 ± 0.07 vs. 0.90 ± 0.14 nmol/mg protein, p = 0.004) and aorta (2.98±0.56 vs. 6.15±0.74 nmol/mg protein, p = 0.011) tissues. Nitrate therapy restored heart nitric oxide metabolite levels decreased by fetal hypothyroidism, while L-arginine administration further decreased aorta nitric oxide metabolite levels. Sodium nitrate increased and L-arginine decreased serum nitric oxide metabolite levels in both control and fetal hypothyroid animals. In conclusion, nitrate therapy restores decreased heart nitric oxide metabolite levels, whereas L-arginine decreases aorta nitric oxide metabolite levels even further in fetal hypothyroid rats, findings relevant to the cardiovascular consequences of congenital hypothyroidism in adulthood.

  8. Long-term oral administration of glucosamine or chondroitin sulfate reduces destruction of cartilage and up-regulation of MMP-3 mRNA in a model of spontaneous osteoarthritis in Hartley guinea pigs.

    PubMed

    Taniguchi, Shin; Ryu, Junnosuke; Seki, Masayuki; Sumino, Takanobu; Tokuhashi, Yasuaki; Esumi, Mariko

    2012-05-01

    Histological and molecular changes were examined to investigate the effects of long-term administration of glucosamine (GlcN) and chondroitin sulfate (CS) in a model of spontaneous osteoarthritis (OA) in Hartley guinea pigs. Three groups of female 3-week-old Hartley guinea pigs received GlcN, CS, and neither agent, respectively. Five animals in each group were sacrificed at 8, 12, and 18 months of age. At 8 months of age, Hartley guinea pigs had severe degeneration of knee joint cartilage, chondrocyte apoptosis, marked reduction of tissue total RNA, decreases of aggrecan and collagen type 2 mRNAs, and increases in MMP-3 and MMP-8 mRNAs. Long-term administration of GlcN and CS reduced cartilage degeneration at 8 months of age. The marked loss of total RNA and the increase in MMP-3 mRNA were also inhibited by GlcN and CS. Thus, long-term oral administration of GlcN or CS inhibits OA progression, maintains total RNA and down-regulates MMP-3 mRNA in a spontaneous OA model in Hartley guinea pigs.

  9. l-Arginine currents in rat cardiac ventricular myocytes

    PubMed Central

    Peluffo, R Daniel

    2007-01-01

    l-Arginine (l-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import l-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel l-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular l-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent l-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of l-Arg. The inward movement of Arg molecules was found to be passive and independent of Na2+, K2+, Ca2+ and Mg2+. The process displayed saturation and membrane potential (Vm)-dependent kinetics, with a K0.5 for l-Arg that increased from 5 mm at hyperpolarizing Vm to 20 mm at +40 mV. l-Lysine and l-ornithine but not d-Arg produced currents with characteristics similar to that activated by l-Arg indicating that the transport process is stereospecific for cationic l-amino acids. l-Arg current was fully blocked after brief incubation with 0.2 mmN-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y2+ family of transporters is responsible for l-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold. PMID:17303641

  10. Caution should be used in long-term treatment with oral compounds of hyaluronic acid in patients with a history of cancer.

    PubMed

    Simone, Procopio; Alberto, Migliore

    2015-11-01

    Intra-articular administration of hyaluronic acid is a valuable therapeutic tool for the management of patients with osteoarthritis. However, in recent years numerous formulations containing hyaluronic acid administrable by oral route have entered the market. Even if there are some data in the literature that have shown their effectiveness, systemic administration may expose a greater risk in certain situations. In fact, although hyaluronic acid is not considered a drug it is certain that it can interact with specific receptors and promote cell proliferation. This interaction may be potentially hazardous in cancer patients for which these oral formulations should be contraindicated.

  11. Long-term contraceptives.

    PubMed

    Brown, Audrey

    2010-10-01

    To avoid unintended pregnancy, women in the UK need to consistently use reliable contraception for over 30 years. The long-acting reversible contraceptive methods compromise the progestogen-only implant, the progestogen-only injectable contraceptive, the copper-bearing intra-uterine device and the levonorgestrel-releasing intra-uterine system. These methods of contraception are highly reliable in pregnancy prevention, and are amongst the medically safest methods for users. Despite this, these long-acting methods are used by less than 10% of the UK population. National guidance has advised that increasing uptake of these long-acting methods will reduce the unplanned pregnancy rate. In addition, these methods are more cost effective than the oral contraceptive even at 1 year of use. Obstetricians and gynaecologists frequently come into contact with women requiring contraceptive advice, and should have a sound knowledge of the long-acting methods.

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

    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.

  13. Methylglyoxal (MG) and cerebro-renal interaction: does long-term orally administered MG cause cognitive impairment in normal Sprague-Dawley rats?

    PubMed

    Watanabe, Kimio; Okada, Kana; Fukabori, Ryoji; Hayashi, Yoshimitsu; Asahi, Koichi; Terawaki, Hiroyuki; Kobayashi, Kazuto; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-01-07

    Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4-6 months of age) and late phase (7-12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

  14. The role of L-arginine and neutrophils on incisional wound healing.

    PubMed

    Cantürk, N Z; Vural, B; Cantürk, Z; Esen, N; Vural, S; Solakoglu, S; Kirkal, G

    2001-12-01

    Although arginine plays an important role in many aspects of inflammation and wound healing, the mechanism is not clear. We aimed to evaluate the effect of L-arginine administration on wound healing and neutrophil activity and on the interaction of these effects. Sixteen rats were divided into two groups: control group and L-arginine group. L-arginine was given intraperitoneally. The rats underwent incisional wounding and were killed on the 7th day of wounding. Blood neutrophil counts, neutrophil adhesivity index, tensile strengths and hydroxyproline level of skin were determined, histopathological and electron microscopical evaluation of healing was performed. Wound scores in the control group were significantly lower (p < 0.05). Hydroxyproline and collagen levels of skin were significantly increased in the L-arginine group (p < 0.05). Blood neutrophil counts and neutrophil adhesivity index in the L-arginine group were significantly increased (p < 0.05), as were the inflammatory cells in the skin. L-arginine may be used during the first phase of healing to induce inflammation in high risk patients.

  15. Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.

    PubMed

    Bayerle-Eder, Michaela; Fuchsjäger-Mayrl, Gabriele; Sieder, Anna; Polska, Elzbieta; Roden, Michael; Stulnig, Thomas; Bischof, Martin G; Waldhäusl, Werner; Schmetterer, Leopold; Wolzt, Michael

    2002-01-01

    Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.

  16. Long-term exposure to oral methylphenidate or dl-amphetamine mixture in peri-adolescent rhesus monkeys: effects on physiology, behavior, and dopamine system development.

    PubMed

    Soto, Paul L; Wilcox, Kristin M; Zhou, Yun; Kumar, Anil; Ator, Nancy A; Riddle, Mark A; Wong, Dean F; Weed, Michael R

    2012-11-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 per group) consumed either an unadulterated orange-flavored solution, a methylphenidate solution, or a dl-amphetamine mixture. Doses were titrated to reach blood/plasma levels comparable to therapeutic levels in children. [¹¹C]MPH and [¹¹C]raclopride dynamic PET scans were performed to image dopamine transporter and D₂-like receptors, respectively. Binding potential (BP(ND)), an index of tracer-specific binding, and amphetamine-induced changes in BP(ND) of [¹¹C]raclopride were estimated by kinetic modeling. There were no consistent differences among groups on the vast majority of measures, including cognitive (psychomotor speed, timing, inhibitory control, cognitive flexibility), general activity, physiological (body weight, head circumference, crown-to-rump length), and neurochemical (ie, developmental changes in dopamine transporter, dopamine D₂ receptor density, and amphetamine-stimulated dopamine release were as expected). Cytogenetic studies indicated that neither drug was a clastogen in rhesus monkeys. Thus, methylphenidate and amphetamine at therapeutic blood/plasma levels during peri-adolescence in non-human primates have little effect on physiological or behavioral/cognitive development.

  17. Long-term oral calcium supplementation reduces diastolic blood pressure in end stage renal disease. A randomized, double-blind, placebo controlled study.

    PubMed

    Petersen, L J; Rudnicki, M; Højsted, J

    1994-01-01

    Previous studies suggest that oral calcium supply reduces blood pressure in patients with mild to moderate hypertension. The aim of this study was to determine whether oral calcium supply reduces blood pressure in patients undergoing haemodialysis. The study was randomized, double-blind, and placebo controlled. Eleven patients received two grams of calcium per day and 12 patients received placebo. Three patients (one from the calcium group and two from the placebo group) dropped out within the first month. The groups were comparable at inclusion regarding blood pressure, weight, and serum values. Blood pressure measurements were auscultatory with a mercury manometer and diastolic blood pressure was measured as Korotkoff phase V. At inclusion a significant positive correlation between serum phosphate and blood pressure was found. After a study period of six months a significant reduction in diastolic blood pressure was found between the two groups (p < 0.05), but no difference was found in systolic blood pressure. The reduction in diastolic blood pressure was 6.9 mmHg of the pretreatment level in the calcium group. In conclusion, the treatment of secondary hyperparathyroidism with oral calcium gives good benefits in the regulation of diastolic blood pressure. A well controlled phosphate homeostasis may also be of importance for the control of blood pressure in haemodialysis patients.

  18. Long-term environmental stewardship.

    SciTech Connect

    Nagy, Michael David

    2010-08-01

    The purpose of this Supplemental Information Source Document is to effectively describe Long-Term Environmental Stewardship (LTES) at Sandia National Laboratories/New Mexico (SNL/NM). More specifically, this document describes the LTES and Long-Term Stewardship (LTS) Programs, distinguishes between the LTES and LTS Programs, and summarizes the current status of the Environmental Restoration (ER) Project.

  19. Long-term urethral catheterisation.

    PubMed

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  20. Long-term oral intake of aluminium or zinc does not accelerate Alzheimer pathology in AβPP and AβPP/tau transgenic mice.

    PubMed

    Akiyama, Haruhiko; Hosokawa, Masato; Kametani, Fuyuki; Kondo, Hiromi; Chiba, Momoko; Fukushima, Masako; Tabira, Takeshi

    2012-08-01

    Whether or not the oral intake of metals such as aluminium (Al) and zinc (Zn) is a risk for Alzheimer's disease (AD) has been a matter of controversy. Lack of AD pathology in patients with Al encephalopathy indicates Al does not cause AD. On the other hand, some epidemiological studies have suggested high Al increases the occurrence of AD. Our purpose is to test if high Al in drinking water is a risk factor for AD. We administered Al and Zn in drinking water to Tg2576, a transgenic mouse model for amyloid β-protein (Aβ) deposition with the Aβ precursor protein (AβPP) mutations (K670N/M671L), and Tg2576/tau(P301L), a model for Aβ and tau deposition. Deionized water was given to the control Tg2576 and Tg2576/tau. After administration for 4-10 months of approximately 100 mg/kg body weight Al or Zn per day, we were not able to find by quantitative immunohistochemical analyses differences in the deposition of Aβ and tau between the treated and untreated groups. Nor did the Al or Zn treatment affect the amount of soluble Aβ and Aβ*56, an Aβ oligomer, measured by ELISA or immunoblot. The oral intake of excess Al or Zn does not accelerate AD pathology in the transgenic mouse models for Aβ and tau accumulation. Such results do not seem to support the notion that excessive oral intake of Al or Zn is a risk factor for AD.

  1. New Insights into the Methodology of L-Arginine-Induced Acute Pancreatitis

    PubMed Central

    Kui, Balázs; Balla, Zsolt; Vasas, Béla; Végh, Eszter T.; Pallagi, Petra; Kormányos, Eszter S.; Venglovecz, Viktória; Iványi, Béla; Takács, Tamás; Hegyi, Péter; Rakonczay, Zoltán

    2015-01-01

    Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5–30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h., In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L–arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5–8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice. PMID:25688985

  2. Presynaptic long-term plasticity

    PubMed Central

    Yang, Ying; Calakos, Nicole

    2013-01-01

    Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity. PMID:24146648

  3. Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse: Long-term oral administration of several manganese compounds

    SciTech Connect

    Komura, Junko; Sakamoto, Michiko )

    1992-02-01

    This work has identified the relative toxicity of four forms of manganese, using biogenic amine levels, tissue retention, weight gain, and activity scores as criteria. Male mice were chronically treated with four forms of manganese administered orally, mixed with the diet, for 12 months. The Mn levels were higher in some parts of brain after feeding insoluble salts than after the soluble salts. The concentration of manganese was significantly increased in the liver and spleen of the manganese carbonate-exposed group, compared with the concentration in the control group. Manganese dioxide feeding lowered dopamine and increased homovanilic acid. Since manganese dioxide is a powerful oxidizing agent in organic chemistry, it possibly enhanced the oxidative metabolite of dopamine. Accumulation of manganese in the brain correlated with reduced hypothalamic dopamine levels in the manganese acetate-exposed group; and the amount of manganese accumulated correlated with the intensity of suppression of motor activity. These findings indicate that manganese dioxide is more toxic than divalent manganese. Of the divalent manganese compounds, manganese acetate seemed to have the greatest toxic effect.

  4. Novel metabolic roles of L-arginine in body energy metabolism and possible clinical applications.

    PubMed

    Hristina, K; Langerholc, T; Trapecar, M

    2014-01-01

    Although the body can synthesize L-arginine, exogenous supplementation may be sometimes necessary, especially in particular conditions which results in depleted endogenous source. Among diseases and states when exogenous supplementation may be necessary are: burns, severe wounds, infections, insufficient circulation, intensive physical activity or sterility. In recent time, the attention was paid to the use of L-arginine supplementation by athletes during intensive sport activity, to enhance tissue growth and general performance, to potentiate the ergogenic potential and muscle tolerance to high intensive work and gas exchange threshold, to decrease ammonia liberation and recovery performance period and to improve wound healing. High-intensity exercise produces transient hyperammoniemia, presumably due to AMP catabolism. Catabolic pathways of AMP may involve its deamination or dephosphorylation, mainly in order to compensate fall in adenylate enrgy charge (AEC), due to AMP rise. The enzymes of purine metabolism have been documented to be particularly sensitive to the effect of dietary L-arginine supplementation. L-arginine supplementation leads to redirection of AMP deamination on account of increased AMP dephosphorylation and subsequent adenosine production and may increase ATP regeneration via activation of AMP kinase (AMPK) pathway. The central role of AMPK in regulating cellular ATP regeneration, makes this enzyme as a central control point in energy homeostasis. The effects of L-arginine supplementation on energy expenditure were successful independently of age or previous disease, in young sport active, elderly, older population and patients with angina pectoris.

  5. Development and optimization of a novel conductometric bi-enzyme biosensor for L-arginine determination.

    PubMed

    Saiapina, O Y; Dzyadevych, S V; Jaffrezic-Renault, N; Soldatkin, O P

    2012-04-15

    A highly sensitive conductometric biosensor for l-arginine determination was developed by exploiting the unique biorecognition capacities of two enzymes of urea cycle - arginase (E.C. 3.5.3.1) and urease (E.C. 3.5.1.5). The enzymes were co-immobilized in a single bioselective membrane on the working sensor, while a lysine rich bovine serum albumin (BSA) membrane was immobilized on the reference sensor, allowing differential measurements. The optimum percentage ratio of arginase and urease within the bioselective membrane was determined when the biosensor sensitivity to l-arginine and urea was optimum. Analytical characteristics of the conductometric biosensor for l-arginine determination were compared for two types of enzyme immobilization (cross-linking with glutaraldehyde (GA) and entrapment in the polymeric membrane). The optimum features in terms of the sensitivity, the linear range, and the detection limit (4.2 μS/mM, 0.01-4mM, and 5.0 × 10(-7)M, respectively) were found for l-arginine biosensor based on enzyme cross-linking with GA. A quantitative determination of l-arginine in the real sample (a drinkable solution "Arginine Veyron") gave a satisfactory result compared to the data provided by the producer (a relative error was 4.6%). The developed biosensor showed high operational and storage stability.

  6. L-arginine pretreatment reduces intestinal mucositis as induced by 5-FU in mice.

    PubMed

    Leocádio, Paola C L; Antunes, Maísa M; Teixeira, Lílian G; Leonel, Alda J; Alvarez-Leite, Jacqueline I; Machado, Denise C C; Generoso, Simone V; Cardoso, Valbert N; Correia, Maria Isabel T D

    2015-01-01

    Beneficial effects of L-arginine on immune responses and bowel function have been reported. Mucositis is a side effect of chemotherapy treatment that affects approximately 40% of patients. This complication is characterized by inflammation that affects the gastrointestinal tract, increasing permeability and causing abdominal pain, nausea, vomiting, and diarrhea, which worsen the patient's nutritional status and increases morbimortality. The aim of this study was to evaluate the effect of pretreating with 2% L-arginine supplementation in water on mucositis as induced by 5-fluorouracil (5-FU; a single dose of 200 mg/kg body weight) in Swiss male mice. The effect of L-arginine on weight, intestinal permeability, morphology, and the histopathological score of the small intestine (from 0 to 12), oxidative stress, myeloperoxidase (MPO), and N-acetylglucosaminidase (NAG) activities were evaluated. Intestinal length improvement was observed, in addition to the partial recovery of the mucosal architecture. L-arginine attenuated the histopathological score and MPO activity. There was also an improvement in intestinal permeability, despite weight loss after 5-FU administration. In conclusion, L-arginine can positively impact intestinal mucositis by promoting partial mucosal recovery, reducing inflammation and improving intestinal permeability.

  7. Jejunal water and electrolyte secretion induced by L-arginine in man.

    PubMed Central

    Hegarty, J E; Fairclough, P D; Clark, M L; Dawson, A M

    1981-01-01

    In this study a perfusion technique has been used to investigate jejunal secretion in response to the dibasic amino acid L-arginine. L-arginine at 5, 15, and 40 mmol/l in isotonic saline solutions induced net intestinal secretion of water and Na+. The structurally similar dibasic amino acid L-lysine caused net absorption at 5 and 15 mmol/l, and only modest net secretion of water and Na+ at 40 mmol/l, although absorption rates of the two amino acids were similar. D-arginine (15 mmol/l) was without effect on net water and Na+ absorption. L-arginine 15 mmol/l inhibited glucose-stimulated water and Na+ absorption when perfused in the same intestinal segment, but was without effect when perfused in separate jejunal or ileal segments. Parenteral chlorpromazine inhibited L-arginine induced jejunal water and Na+ secretion. Jejunal secretion induced by L-arginine thus appears not to be due to passive osmotic water flow, nor to release of circulating secretagogues. Stimulation of a mucosal secretory process is most likely to be the mechanism. PMID:6783480

  8. Long term complications of diabetes

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  9. Endogenous Inactivators of Arginase, l-Arginine Decarboxylase, and Agmatine Amidinohydrolase in Evernia prunastri Thallus 1

    PubMed Central

    Legaz, María Estrella; Vicente, Carlos

    1983-01-01

    Arginase (EC 3.5.3.1), l-arginine decarboxylase (EC 4.1.1.19), and agmatine amidinohydrolase (EC 3.5.3.11) activities spontaneously decay in Evernia prunastri thalli incubated on 40 millimolar l-arginine used as inducer of the three enzymes if dithiothreitol is not added to the media. Lichen thalli accumulate both chloroatranorin and evernic acid in parallel to the loss of activity. These substances behave as inactivators of the enzymes at a range of concentrations between 2 and 20 micromolar, whereas several concentrations of dithiothreitol reverse, to some extent, the in vitro inactivation. PMID:16662821

  10. Endogenous Inactivators of Arginase, l-Arginine Decarboxylase, and Agmatine Amidinohydrolase in Evernia prunastri Thallus.

    PubMed

    Legaz, M E; Vicente, C

    1983-02-01

    Arginase (EC 3.5.3.1), l-arginine decarboxylase (EC 4.1.1.19), and agmatine amidinohydrolase (EC 3.5.3.11) activities spontaneously decay in Evernia prunastri thalli incubated on 40 millimolar l-arginine used as inducer of the three enzymes if dithiothreitol is not added to the media. Lichen thalli accumulate both chloroatranorin and evernic acid in parallel to the loss of activity. These substances behave as inactivators of the enzymes at a range of concentrations between 2 and 20 micromolar, whereas several concentrations of dithiothreitol reverse, to some extent, the in vitro inactivation.

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

    PubMed

    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.

  12. Long-term parenteral nutrition

    PubMed Central

    Ladefoged, Karin; Jarnum, Stig

    1978-01-01

    Nineteen patients (11 women and eight men) aged 20-68 received long-term parenteral nutrition, mostly at home, for six to 63 months (mean 19 months). Indications for LTPN were extensive, active Crohn's disease in three patients, intestinocutaneous fistulas in three, and short-bowel syndrome in the remaining 13 patients. Subclavian or intra-atrial (Broviac) catheters were most commonly used, for which the average life was four and seven months respectively. Complications of long-term parenteral nutrition included pneumothorax in four out of 48 subclavian vein punctures. Catheter-induced thrombosis of central veins was shown by phlebography 17 times in nine patients, and eight episodes of total occlusion occurred. Two of these patients had pulmonary infarction. Nineteen episodes of catheter sepsis occurred in 11 patients, but only one was fatal. Complications related to intestinal disease included intra-abdominal abscesses and intestinal fistulas, and disturbances of liver function. Five patients died, though in only two was death related to long-term parenteral nutrition. One of these patients died from catheter sepsis, the other had subdural haematoma possibly caused by anticoagulant treatment. Eight of the 14 surviving patients still needed parenteral nutrition. All received a disability pension, but six had an acceptable quality of life with almost normal social activities. Despite problems such as difficulties in maintaining standardised infusion programmes, it was concluded that long-term parenteral nutrition at home is practicable and consistent with an acceptable quality of life. ImagesFIG 2 PMID:98199

  13. Role of Environmental Conditions on the Interaction of L-Arginine with Oxide Mineral Surfaces

    NASA Astrophysics Data System (ADS)

    Klochko, K.; Jonsson, C. M.; Jonsson, C. L.; Lee, N.; Cleaves, H. J., II; Sverjensky, D. A.; Hazen, R. M.

    2010-04-01

    The current study is focused on surface interactions between L-arginine, the most basic protein amino acid, and rutile in NaCl media over a wide range of solution pH conditions, amino acid concentrations, and solution ionic strengths.

  14. Home management of INR in the public health system: feasibility of self-management of oral anticoagulation and long-term performance of individual POC devices in determining INR.

    PubMed

    da Silva Saraiva, Sabrina; Orsi, Fernanda Andrade; Santos, Marcos Pereira; Machado, Tania; Montalvão, Silmara; Costa-Lima, Carolina; de Paula, Erich Vinícius; Colella, Marina Pereira; Annichino-Bizzacchi, Joyce

    2016-07-01

    The home prothrombin time/international normalized ratio (PT/INR) self-management could be convenient for patients, enhancing treatment compliance and improving the quality of the oral anticoagulation. However, patient self-management (PSM) of oral anticoagulation may not be feasible for up to half of the patients due to cognitive or educational issues. In the present study, we aimed to evaluate the feasibility of a PSM program in a public health medical center that provides care for low-income patients. We also aimed to determine the accuracy of individual point-of-care devices (CoaguChek XS(®)) during long-term of home manipulation. Patients' time-in-therapeutic range (TTR) and perception of quality of life, were evaluated at scheduled study-visits to the center. Additionally, the accuracy of individual CoaguChek XS(®) was evaluated in comparison to the standard automated coagulometer at scheduled study-visits to the center. Twenty-five patients were included in the PSM program. The median TTR of patients was 75 % before inclusion, 72 % at 3 months, 75 % at 6 months and 100 % at 12 months after the beginning of self-management (P = 0.14).The median DASS scores were 64, 63, 61.5 and 71.5 before inclusion and at 3, 6 and 12 months, respectively (P = 0.09). One hundred paired INR values were obtained. Correlation between INR values delivered by individual CoaguChek XS(®) and the automated coagulometer was 94 % and the mean result bias was 0.07 INR units. The coefficient of correlation and the mean bias between methods was stable during 24 months of follow-up. The present study suggests that PSM is feasible for patients treated in the public health system and that the results delivered by CoaguChek XS(®) have long-term reliability.

  15. Long-term management of prolactinomas.

    PubMed

    Schlechte, Janet A

    2007-08-01

    Prolactinomas are a frequent cause of gonadal dysfunction and infertility, especially in young women. The regulation of prolactin secretion and the efficacy of dopamine agonists in the therapy of prolactinomas are well established. The current challenges in management of prolactinomas are related to follow-up after successful therapy. Issues and questions to be addressed in this approach to long-term management of prolactinomas include the frequency of radiographic monitoring, effect of pregnancy and menopause, safety of estrogen in women taking oral contraceptives, and the potential for discontinuation of dopamine agonist therapy.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Mechanisms for Improved Hygroscopicity of L-Arginine Valproate Revealed by X-Ray Single Crystal Structure Analysis.

    PubMed

    Ito, Masataka; Nambu, Kaori; Sakon, Aya; Uekusa, Hidehiro; Yonemochi, Etsuo; Noguchi, Shuji; Terada, Katsuhide

    2017-03-01

    Valproic acid is widely used as an antiepileptic agent. Valproic acid is in liquid phase while sodium valproate is in solid phase at room temperature. Sodium valproate is hard to manufacture because of its hygroscopic and deliquescent properties. To improve these, cocrystal and salt screening for valproic acid was employed in this study. Two solid salt forms, l-arginine valproate and l-lysine valproate, were obtained and characterized. By using dynamic vapor sorption method, the critical relative humidity of sodium valproate, l-arginine valproate, and l-lysine valproate were measured. Critical relative humidity of sodium valproate was 40%, of l-lysine valproate was 60%, and of l-arginine valproate was 70%. Single-crystal X-ray structure determination of l-arginine valproate was employed. l-Lysine valproate was of low diffraction quality, and l-arginine valproate formed a 1:1 salt. Crystal l-arginine valproate has a disorder in the methylene carbon chain that creates 2 conformations. The carboxylate group of valproic acid is connected to the amino group of l-arginine. Crystalline morphologies were calculated from its crystal structure. Adsorption of water molecules to crystal facets was simulated by Material Studio. When comparing adsorption energy per site of these salts, sodium valproate is more capable of adsorption of water molecule than l-arginine valproate.

  18. Effect of l-Arginine in One Patient with Peroxisome Biogenesis Disorder due to PEX12 Deficiency.

    PubMed

    Sorlin, Arthur; Briand, Gilbert; Cheillan, David; Wiedemann, Arnaud; Montaut-Verient, Bettina; Schmitt, Emmanuelle; Feillet, François

    2016-06-01

    Peroxisome biogenesis disorders (PBD) are a heterogeneous group of disorders due to PEX genes mutations, with a broad clinical spectrum comprising severe neonatal disease to mild presentation. Recently, Berendse et al reported an improvement of peroxisomal functions with l-arginine supplementation in fibroblasts with specific mutations of PEX1, PEX6, and PEX12. We report the first treatment by l-arginine in a patient homozygous for the specific PEX12 mutation shown to be l-arginine responsive in fibroblasts. We described the effect of l-arginine on biochemical (decrease of some plasma peroxisomal parameters) and neurophysiological (improvement of deafness) parameters. Some subjective clinical effects have also been observed (no more sialorrhea, behavior improvement). More studies are needed to assess the efficacy of l-arginine in some PBD patients with specific mutations.

  19. Long-term data archiving

    SciTech Connect

    Moore, David Steven

    2009-01-01

    Long term data archiving has much value for chemists, not only to retain access to research and product development records, but also to enable new developments and new discoveries. There are some recent regulatory requirements (e.g., FDA 21 CFR Part 11), but good science and good business both benefit regardless. A particular example of the benefits of and need for long term data archiving is the management of data from spectroscopic laboratory instruments. The sheer amount of spectroscopic data is increasing at a scary rate, and the pressures to archive come from the expense to create the data (or recreate it if it is lost) as well as its high information content. The goal of long-term data archiving is to save and organize instrument data files as well as any needed meta data (such as sample ID, LIMS information, operator, date, time, instrument conditions, sample type, excitation details, environmental parameters, etc.). This editorial explores the issues involved in long-term data archiving using the example of Raman spectral databases. There are at present several such databases, including common data format libraries and proprietary libraries. However, such databases and libraries should ultimately satisfy stringent criteria for long term data archiving, including readability for long times into the future, robustness to changes in computer hardware and operating systems, and use of public domain data formats. The latter criterion implies the data format should be platform independent and the tools to create the data format should be easily and publicly obtainable or developable. Several examples of attempts at spectral libraries exist, such as the ASTM ANDI format, and the JCAMP-DX format. On the other hand, proprietary library spectra can be exchanged and manipulated using proprietary tools. As the above examples have deficiencies according to the three long term data archiving criteria, Extensible Markup Language (XML; a product of the World Wide Web

  20. Acute and long-term effects of once-daily oral bromocriptine and a new long-acting non-ergot dopamine agonist, quinagolide, in the treatment of hyperprolactinemia: a double-blind study.

    PubMed

    Verhelst, J A; Froud, A L; Touzel, R; Wass, J A; Besser, G M; Grossman, A B

    1991-10-01

    Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

  1. Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

    PubMed

    Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

    1999-12-01

    Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

  2. Comparative effects of sildenafil, phentolamine, yohimbine and L-arginine on the rabbit corpus cavernosum.

    PubMed

    Sharabi, F M; Daabees, T T; El-Metwally, M A; Senbel, A M

    2004-04-01

    Penile erection involves relaxation of smooth muscle of corpus cavernosum and associated arterioles. Sildenafil, a highly selective inhibitor of phosphodiesterase type 5, is effective in the treatment of erectile dysfunction. The aim of this study is to investigate the effect of sildenafil on smooth muscle of the rabbit corpus cavernosum (RCC) and to compare its effect with those of phentolamine, yohimbine and L-arginine. The effects of sildenafil, phentolamine, yohimbine and L-arginine were studied on the response of the RCC to electrical field stimulation (EFS) as well as on the phenylephrine (PE, 3 x 10(-6) M)-induced tone. EFS caused transient, frequency-dependent relaxation of the RCC that was inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine (3 x 10(-5) M). Sildenafil (1 x 10(-9)-1 x 10(-6) M) and phentolamine (1 x 10(-9)-1 x 10(-6) M) enhanced the EFS-induced relaxation in a concentration-dependent manner with ED50 of 0.056 +/- 0.004 and 0.572 +/-0.035 microM at 8 Hz, respectively, yohimbine (3 x 10(-7)-3 x 10(-5) M) and L-arginine (3 x 10(-6)-3 x 10(-4) M) did not show significant effects (ED50 at 8 Hz = 35.84 +/-2.24 and 2.164 +/- 0.174 microM, respectively). Sildenafil (1 x 10(-9) and 1 x 10(-8) M) potentiated the EFS-induced relaxation caused by L-arginine (3 x 10(-5) m). Sildenafil, phentolamine, yohimbine and L-arginine reduced the PE-induced tone to different extents; the ED50 values were 0.81 +/- 0.097, 0.49 +/- 0.025 and 13.97 +/- 1.10 microM, respectively. Maximum concentration of L-arginine used failed to produce 50% relaxation (ED20 = 221.82 +/- 15.71 microM). The muscle relaxant effects of different combinations of sildenafil and L-arginine on PE-induced tone did not differ significantly from the sum of the individual effects. The results demonstrate that sildenafil, when compared to other drugs used in penile erection dysfunction, shows the highest potency on the nitrergic transmission in the RCC. On the other hand

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

    PubMed Central

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

    2015-01-01

    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 < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine 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

  4. AMP-activated protein kinase regulates L-arginine mediated cellular responses

    PubMed Central

    2013-01-01

    Background Our prior study revealed the loss in short-term L-Arginine (ARG) therapeutic efficacy after continuous exposure; resulting in tolerance development, mediated by endothelial nitric oxide synthase (eNOS) down-regulation, secondary to oxidative stress and induced glucose accumulation. However, the potential factor regulating ARG cellular response is presently unknown. Method Human umbilical vein endothelial cells were incubated with 100 μM ARG for 2 h in buffer (short-term or acute), or for 7 days in culture medium and challenged for 2 h in buffer (continuous or chronic), in the presence or absence of other agents. eNOS activity was determined by analyzing cellular nitrite/nitrate (NO2–/NO3–), and AMP-activated protein kinase (AMPK) activity was assayed using SAMS peptide. 13C6 glucose was added to medium to measure glucose uptake during cellular treatments, which were determined by LC-MS/MS. Cellular glucose was identified by o-toluidine method. Superoxide (O2•–) was identified by EPR-spin-trap, and peroxynitrite (ONOO–) was measured by flow-cytometer using aminophenyl fluorescein dye. Results Short-term incubation of cells with 100 μM ARG in the presence or absence of 30 μM L-NG-Nitroarginine methyl ester (L-NAME) or 30 μM AMPK inhibitor (compound C, CMP-C) increased cellular oxidative stress and overall glucose accumulation with no variation in glucose transporter-1 (GLUT-1), or AMPK activity from control. The increase in total NO2–/NO3– after 2 h 100 μM ARG exposure, was suppressed in cells co-incubated with 30 μM CMP-C or L-NAME. Long-term exposure of ARG with or without CMP-C or L-NAME suppressed NO2–/NO3–, glucose uptake, GLUT-1, AMPK expression and activity below control, and increased overall cellular glucose, O2•– and ONOO–. Gluconeogenesis inhibition with 30 μM 5-Chloro-2-N-2,5-dichlorobenzenesulfonamido-benzoxazole (CDB) during ARG exposure for 2 h maintained overall cellular glucose to control, but increased

  5. Nanoscale characterization of effect of L-arginine on Streptococcus mutans biofilm adhesion by atomic force microscopy.

    PubMed

    Sharma, Shivani; Lavender, Stacey; Woo, JungReem; Guo, Lihong; Shi, Wenyuan; Kilpatrick-Liverman, LaTonya; Gimzewski, James K

    2014-07-01

    A major aetiological factor of dental caries is the pathology of the dental plaque biofilms. The amino acid L-arginine (Arg) is found naturally in saliva as a free molecule or as a part of salivary peptides and proteins. Plaque bacteria metabolize Arg to produce alkali and neutralize glycolytic acids, promoting a less cariogenous oral microbiome. Here, we explored an alternative and complementary mechanism of action of Arg using atomic force microscopy. The nanomechanical properties of Streptococcus mutans biofilm extracellular matrix were characterized under physiological buffer conditions. We report the effect of Arg on the adhesive behaviour and structural properties of extracellular polysaccharides in S. mutans biofilms. High-resolution imaging of biofilm surfaces can reveal additional structural information on bacterial cells embedded within the surrounding extracellular matrix. A dense extracellular matrix was observed in biofilms without Arg compared to those grown in the presence of Arg. S. mutans biofilms grown in the presence of Arg could influence the production and/or composition of extracellular membrane glucans and thereby affect their adhesion properties. Our results suggest that the presence of Arg in the oral cavity could influence the adhesion properties of S. mutans to the tooth surface.

  6. A novel prokaryotic L-arginine:glycine amidinotransferase is involved in cylindrospermopsin biosynthesis.

    PubMed

    Muenchhoff, Julia; Siddiqui, Khawar S; Poljak, Anne; Raftery, Mark J; Barrow, Kevin D; Neilan, Brett A

    2010-09-01

    We report the first characterization of an L-arginine:glycine amidinotransferase from a prokaryote. The enzyme, CyrA, is involved in the pathway for biosynthesis of the polyketide-derived hepatotoxin cylindrospermopsin from Cylindrospermopsis raciborskii AWT205. CyrA is phylogenetically distinct from other amidinotransferases, and structural alignment shows differences between the active site residues of CyrA and the well-characterized human L-arginine:glycine amidinotransferase (AGAT). Overexpression of recombinant CyrA in Escherichia coli enabled biochemical characterization of the enzyme, and we confirmed the predicted function of CyrA as an L-arginine:glycine amidinotransferase by (1) H NMR. As compared with AGAT, CyrA showed narrow substrate specificity when presented with substrate analogs, and deviated from regular Michaelis-Menten kinetics in the presence of the non-natural substrate hydroxylamine. Studies of initial reaction velocities and product inhibition, and identification of intermediate reaction products, were used to probe the kinetic mechanism of CyrA, which is best described as a hybrid of ping-pong and sequential mechanisms. Differences in the active site residues of CyrA and AGAT are discussed in relation to the different properties of both enzymes. The enzyme had maximum activity and maximum stability at pH 8.5 and 6.5, respectively, and an optimum temperature of 32 °C. Investigations into the stability of the enzyme revealed that an inactivated form of this enzyme retained an appreciable amount of secondary structure elements even on heating to 94 °C, but lost its tertiary structure at low temperature (T(max) of 44.5 °C), resulting in a state reminiscent of a molten globule. CyrA represents a novel group of prokaryotic amidinotransferases that utilize arginine and glycine as substrates with a complex kinetic mechanism and substrate specificity that differs from that of the eukaryotic L-arginine:glycine amidinotransferases.

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

    PubMed

    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.

  8. The protective effects of long-term oral administration of marine collagen hydrolysate from chum salmon on collagen matrix homeostasis in the chronological aged skin of Sprague-Dawley male rats.

    PubMed

    Liang, Jiang; Pei, Xinrong; Zhang, Zhaofeng; Wang, Nan; Wang, Junbo; Li, Yong

    2010-10-01

    To investigate the long-term effects of marine collagen hydrolysate (MCH) from Chum Salmon skin on the aberrant collagen matrix homeostasis in chronological aged skin, Sprague-Dawley male rats of 4-wk-old were orally administrated with MCH at the diet concentrations of 2.25% and 4.5% for 24 mo. Histological and biochemical analysis revealed that MCH had the potential to inhibit the collagen loss and collagen fragmentation in chronological aged skin. Based on immunohistochemistry and western blot analysis, collagen type I and III protein expression levels in MCH-treated groups significantly increased as compared with the aged control group. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed MCH was able to increase the expressions of procollagen type I and III mRNA (COL1A2 and COL3A1) through activating Smad signaling pathway with up-regulated TGF-βRII (TβRII) expression level. Meanwhile, MCH was shown to inhibit the age-related increased collagen degradation through attenuating MMP-1 expression and increasing tissue inhibitor of metalloproteinases-1 expression in a dose-dependent manner. Moreover, MCH could alleviate the oxidative stress in chronological aged skin, which was revealed from the data of superoxide dismutase activity and the thiobarbituric acid reactive substances level in skin homogenates. Therefore, MCH was demonstrated to have the protective effects on chronological skin aging due to the influence on collagen matrix homeostasis. And the antioxidative property of MCH might play an important role in the process.

  9. [Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors. Proposals of the Working Group on Perioperative Haemostasis (GIHP) - March 2013].

    PubMed

    Pernod, G; Albaladejo, P; Godier, A; Samama, C M; Susen, S; Gruel, Y; Blais, N; Fontana, P; Cohen, A; Llau, J V; Rosencher, N; Schved, J F; de Maistre, E; Samama, M M; Mismetti, P; Sié, P

    2013-10-01

    New direct oral anticoagulants (NOAC), inhibitors of factor IIa or Xa, are expected to be widely used for the treatment of venous thromboembolic disease, or in case of atrial fibrillation. Such anticoagulant treatments are known to be associated with haemorrhagic complications. Moreover, it is likely that such patients on long-term treatment with NOAC will be exposed to emergency surgery or invasive procedures. Due to the present lack of experience in such conditions, we cannot make recommendations, but only propose management for optimal safety as regards the risk of bleeding in such emergency conditions. In this article, only dabigatran and rivaroxaban were discussed. For emergency surgery at risk of bleeding, we propose to dose the plasmatic concentration of drug. Levels inferior or equal to 30ng/mL for both dabigatran and rivaroxaban, should enable the realization of a high bleeding risk surgery. For higher concentration, it was proposed to postpone surgery by monitoring the evolution of the drug concentration. Action is then defined by the kind of NOAC and its concentration. If the dosage of the drug is not immediately available, proposals only based on the usual tests, PT and aPTT, also are presented. However, these tests do not really assess drug concentration or bleeding risk. In case of severe haemorrhage in a critical organ, it is proposed to reduce the effect of anticoagulant therapy using a nonspecific procoagulant drug (activated prothrombin concentrate, FEIBA, 30-50U/kg, or non-activated 4-factors prothrombin concentrates 50U/kg). For any other type of severe haemorrhage, the administration of such a procoagulant drug, potentially thrombogenic in these patients, will be discussed regarding concentration of NACO and possibilities for mechanical haemostasis.

  10. [Blood monocytic L-arginine metabolic changes in diabetic foot syndrome].

    PubMed

    Barinov, E F; Sulaeva, O N; Barinova, M E

    2010-05-01

    An inhibition test was used to study mechanisms responsible for L-arginine metabolic disturbances in the blood monocytes of patients with diabetic foot syndrome (DFS). It showed enhanced baseline iNOS activity and inhibition of the arginase pathway with lower nitrite production in response to the administration of lipopolysaccharide in the monocytes of patients with DFS. Impaired L-arginine metabolism was related to the higher activities of protein kinase C (PKC), phosphodiesterase (PDE), and 5-lipoxygenase (5-LO) along with decreased cyclooxygenase activity and drastic protein kinase A (PKA) inhibition. Within the first week, no changes in the wound process were associated with persistent metabolic disturbances of arachidonic acid and serine-threonine kinases with the higher sensitivity of AT1 receptors. In patients with DFS, the condition for wound process termination was decreased baseline iNOS activity and enhanced arginase-1 activity during PKA stimulation with the lower activity of 5-LO, PDE, and PKS. However, impaired mechanisms in the regulation of monocytic L-arginine metabolism persisted even a month later, which predetermines skin remodeling disturbance and the likelihood of recurrent DFS

  11. Pathogenesis and treatment of the cardiorenal syndrome: Implications of L-arginine-nitric oxide pathway impairment.

    PubMed

    Rajapakse, Niwanthi W; Nanayakkara, Shane; Kaye, David M

    2015-10-01

    A highly complex interplay exists between the heart and kidney in the setting of both normal and abnormal physiology. In the context of heart failure, a pathophysiological condition termed the cardiorenal syndrome (CRS) exists whereby dysfunction in the heart or kidney can accelerate pathology in the other organ. The mechanisms that underpin CRS are complex, and include neuro-hormonal activation, oxidative stress and endothelial dysfunction. The endothelium plays a central role in the regulation of both cardiac and renal function, and as such impairments in endothelial function can lead to dysfunction of both these organs. In particular, reduced bioavailability of nitric oxide (NO) is a key pathophysiologic component of endothelial dysfunction. The synthesis of NO by the endothelium is critically dependent on the plasmalemmal transport of its substrate, L-arginine, via the cationic amino acid transporter-1 (CAT1). Impaired L-arginine-NO pathway activity has been demonstrated individually in heart and renal failure. Recent findings suggest abnormalities of the L-arginine-NO pathway also play a role in the pathogenesis of CRS and thus this pathway may represent a potential new target for the treatment of heart and renal failure.

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

    PubMed

    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.

  13. Continuous Exposure to L-Arginine Induces Oxidative Stress and Physiological Tolerance in Cultured Human Endothelial Cells

    PubMed Central

    Mohan, Srinidi; Wu, Chia-Ching; Shin, Soyoung; Fung, Ho-Leung

    2011-01-01

    The therapeutic benefits of L-arginine (ARG) supplementation in humans, often clearly observed in short-term studies, are not evident after long-term use. The mechanisms for the development of ARG tolerance are not known and cannot be readily examined in humans. We have developed a sensitive in vitro model using a low glucose/low arginine culture medium to study the mechanisms of ARG action and tolerance using two different human endothelial cells, i.e., Ea.hy926 and human umbilical venous endothelial cells (HUVEC). Cultured cells were incubated with different concentrations of ARG and other agents to monitor their effects on eNOS expression and function, as well as glucose and superoxide (O2•−) accumulation. Short-term (2 h) exposure to at least 50 μM ARG moderately increased eNOS activity and intracellular glucose (p<0.05), with no change in eNOS mRNA or protein expression. In contrast, 7-day continuous ARG exposure suppressed eNOS expression and activity. This was accompanied by increase in glucose and O2•− accumulation. Co-incubation with 100 μM ascorbic acid, 300 U/ml PEG-superoxide dismutase (PEG-SOD), 100 μM L-lysine or 30 μM 5-chloro-2-(N-2,5-dichlorobenenesulfonamido))-benzoxazole (a fructose-1,6-bisphosphatase inhibitor) prevented the occurrence of cellular ARG tolerance. Short-term co-incubation of ARG with PEG-SOD improved cellular nitrite accumulation without altering cellular ARG uptake. These studies suggest that ARG-induced oxidative stress may be a primary causative factor for the development of cellular ARG tolerance. PMID:22130739

  14. Prevention of muscle fibers atrophy during gravitational unloading: The effect of L-arginine administration

    NASA Astrophysics Data System (ADS)

    Kartashkina, N.; Lomonosova, Y.; Shevchenko, T. F.; Bugrova, A. E.; Turtikova, O. V.; Kalamkarov, G. R.; Nemirovskaya, T. L.

    2011-05-01

    Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor L-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220-230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+ L-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt L-arginine) and 14 days of hindlimb suspension+ L-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group ( p<0.05) and 40% and 25% in the HSN group, as compared to the CTR group ( p<0.05), respectively. CSA of ST and FT muscle fibers were 25% and 16% larger in the HSL group in comparison with the HS group ( p<0.05), respectively. The atrophy of FT muscle fibers in the HSL group was completely prevented since FT fiber CSA had no significant differences from the CTR group. In HS group, the percentage of fibers revealing either gaps/disruption of the dystrophin layer of the myofiber surface membrane increased by 27% and 17%, respectively, as compared to the controls (CTR group, p<0.05). The destructions in dystrophin layer integrity and reductions of desmin content were significantly prevented in HSL group. NO concentration decreased by 60% in the HS group (as well as HSN group) and at the same time no changes were detectable in the HSL group. This fact indicates the compensation of NO content in the unloaded muscle under L-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: L-arginine

  15. [Enteral nutrition through long-term jejunostomy].

    PubMed

    Fernández, T; Neira, P; Enríquez, C

    2008-01-01

    We present the case of a female patient suffering a peritonitis episode after subtotal gastrectomy due to gastric neoplasm in relation to lesser curvature necrosis extending to the anterior esophageal wall. This an uncommon andsevere complication that made mandatory further aggressive surgery: transection of the abdominal esophagus, transection of the gastric stump, and cervical esophagostomy with creation of a jejunostomy with a needle catheter for feeding. This digestive tube access technique is generally used during major abdominal post-surgery until oral intake is reestablished. Our patient has been 187 days with this therapy since reconstruction of the GI tract was ruled out due to tumoral infiltration of the colon and tumor recurrence at the gastrohepatic omentum. To date, there has been no complication from permanence and/or long-term use of this technique.

  16. Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of bis selenide in the mouse tail suspension test.

    PubMed

    Jesse, Cristiano R; Wilhelm, Ethel A; Bortolatto, Cristiani F; Rocha, João B T; Nogueira, Cristina W

    2010-06-10

    The present study investigated a possible antidepressant-like effect of bis selenide by using the forced swimming and the tail suspension tests. The involvement of the l-arginine-nitric oxide-cyclic guanosine monophosphate signaling pathway in the antidepressant-like action of bis selenide was investigated. Bis selenide, given by oral route at doses of 0.5-5mg/kg, decreased the immobility time in the forced swimming and tail suspension tests. Pretreatment with l-arginine (750mg/kg, intraperitoneal, i.p., a nitric oxide precursor), sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor) or S-nitroso-N-acetyl-penicillamine (25microg/site, intracerebroventricular, i.c.v., a nitric oxide donor) reversed the reduction in the immobility time elicited by bis selenide (1mg/kg, p.o.) in the tail suspension test. Bis selenide (0.1mg/kg, p.o., a subeffective dose) produced a synergistic antidepressant-like effect with N(G)-nitro-L-arginine (0.3mg/kg, i.p., an inhibitor of nitric oxide synthase) or 7-nitroindazole (25mg/kg, i.p., a specific neuronal nitric oxide synthase inhibitor) in the tail suspension test. Pretreatment of animals with methylene blue (10mg/kg, i.p., an inhibitor of nitric oxide synthase and soluble guanylate cyclase) or 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (30pmol, i.c.v., a specific inhibitor of soluble guanylate cyclase), at subeffective doses, caused a synergistic effect with bis selenide in the tail suspension test. Bis selenide (1mg/kg, p.o.), at an effective dose in the forced swimming and tail suspension tests, caused a significant decrease in the mouse cerebral nitrate/nitrite levels. The antidepressant-like effect of bis selenide in the tail suspension test is dependent on the inhibition of the L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.

  17. Asthma Medicines: Long-Term Control

    MedlinePlus

    ... Size Email Print Share Asthma Medicines: Long-term Control Page Content Article Body Corticosteroids Synthetic versions of ... form, they are used exclusively for long-term control; they are not very effective for acute symptoms. ...

  18. Long Term Surface Salinity Measurements

    NASA Technical Reports Server (NTRS)

    Schmitt, Raymond W.; Brown, Neil L.

    2005-01-01

    Our long-term goal is to establish a reliable system for monitoring surface salinity around the global ocean. Salinity is a strong indicator of the freshwater cycle and has a great influence on upper ocean stratification. Global salinity measurements have potential to improve climate forecasts if an observation system can be developed. This project is developing a new internal field conductivity cell that can be protected from biological fouling for two years. Combined with a temperature sensor, this foul-proof cell can be deployed widely on surface drifters. A reliable in-situ network of surface salinity sensors will be an important adjunct to the salinity sensing satellite AQUARIUS to be deployed by NASA in 2009. A new internal-field conductivity cell has been developed by N Brown, along with new electronics. This sensor system has been combined with a temperature sensor to make a conductivity - temperature (UT) sensor suitable for deployment on drifters. The basic sensor concepts have been proven on a high resolution CTD. A simpler (lower cost) circuit has been built for this application. A protection mechanism for the conductivity cell that includes antifouling protection has also been designed and built. Mr. A.Walsh of our commercial partner E-Paint has designed and delivered time-release formulations of antifoulants for our application. Mr. G. Williams of partner Clearwater Instrumentation advised on power and communication issues and supplied surface drifters for testing.

  19. AB055. Long term NIV

    PubMed Central

    Siopi, Dimitra

    2016-01-01

    During the last decades, non-invasive mechanical ventilation has evolved into one of the most evidence-based areas of respiratory medicine, with many indications in acute or chronic respiratory failure. From the first application of negative pressure models during poliomyelitis epidemics to the new sophisticated positive pressure models, and the development of the “intelligent ventilators”, there has been a long time course. Undoubtedly the spur was given by better understanding of respiratory physiology during sleep and the shift of healthcare towards a chronic base. Novel randomized controlled trials (RCTs) established the use of NIV in acute respiratory failure due to exacerbations of COPD, as well as acute pulmonary edema and weaning from invasive mechanical ventilation. Long-term NIV has been used in neuromuscular diseases for many decades, first in Duchenne muscular dystrophy, and then spreading to other disorders of this category, increasing survival in inherited neuromuscular diseases. NIV should be initiated early in the course of the disease, when symptomatic nocturnal hypoventilation is detected. Combined with cough augmentation (physiotherapy, insufflation-exsufflation devices) and percutaneous gastrostomy feeding, it can delay tracheostomy and invasive ventilation. In ALS patients NIV improves the quality of life and increases survival, especially when there is no bulbar involvement. The right time to initiate ventilation in this group of patients is not well established since it is difficult to detect signs and symptom of respiratory impairment. Patients seem to benefit from an early application of NIV, and their personal decisions should always be considered before any intervention. In patients with chest wall disorders NIV—despite the fact that RCTs are lacking—has proved its value in many uncontrolled trials and numerous reports. It seems to improve the work of breathing, sleep architecture, nocturnal and daytime arterial blood gases. The

  20. Phase III Multi-Institutional Trial of Adjuvant Chemotherapy With Paclitaxel, Estramustine, and Oral Etoposide Combined With Long-Term Androgen Suppression Therapy and Radiotherapy Versus Long-Term Androgen Suppression Plus Radiotherapy Alone for High-Risk Prostate Cancer: Preliminary Toxicity Analysis of RTOG 99-02

    SciTech Connect

    Rosenthal, Seth A. Bae, Kyoungwha; Pienta, Kenneth J.; Sobczak, Mark L.; Asbell, Sucha O.; Rajan, Raghu; Kerlin, Kevin J.; Michalski, Jeff M.; Sandler, Howard M.

    2009-03-01

    Purpose: Long-term androgen suppression plus radiotherapy (AS+RT) is standard treatment of high-risk prostate cancer. A randomized trial, Radiation Therapy Oncology Group trial 9902, was undertaken to determine whether adjuvant chemotherapy with paclitaxel, estramustine, and etoposide (TEE) plus AS+RT would improve disease outcomes with acceptable toxicity. Methods and Materials: High-risk (prostate-specific antigen 20-100 ng/mL and Gleason score {>=}7; or Stage T2 or greater, Gleason score 8, prostate-specific antigen level <100 ng/mL) nonmetastatic prostate cancer patients were randomized to AS+RT (Arm 1) vs. AS+RT plus four cycles of TEE (Arm 2). TEE was delivered 4 weeks after RT. AS continued for 2 years for both treatment arms. RT began after 8 weeks of AS began. Results: The Radiation Therapy Oncology Group 9902 trial opened January 11, 2000. Excess thromboembolic toxicity was noted, leading to study closure October 4, 2004. A total of 397 patients were accrued, and the data for 381 were analyzable. An acute and long-term toxicity analysis was performed. The worst overall toxicities during treatment were increased for Arm 2. Of the 192 patients, 136 (71%) on Arm 2 had RTOG Grade 3 or greater toxicity compared with 70 (37%) of 189 patients on Arm 1. Statistically significant increases in hematologic toxicity (p < 0.0001) and gastrointestinal toxicity (p = 0.017) but not genitourinary toxicity (p = 0.07) were noted during treatment. Two Grade 5 complications related to neutropenic infection occurred in Arm 2. Three cases of myelodysplasia/acute myelogenous leukemia were noted in Arm 2. At 2 and 3 years after therapy completion, excess long-term toxicity was not observed in Arm 2. Conclusion: TEE was associated with significantly increased toxicity during treatment. The toxicity profiles did not differ at 2 and 3 years after therapy. Toxicity is an important consideration in the design of trials using adjuvant chemotherapy for prostate cancer.

  1. Long-Term Planning in Higher Education.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific and Cultural Organization, Bangkok (Thailand). Principal Regional Office for Asia and the Pacific.

    This report presents the concepts and issues discussed at a Regional Symposium on Long-term Planning in Higher Education held in Dhaka, Bangladesh, September 21-30, 1986. Chapter 1 explores some fundamental issues about the rationale for the objectives of long-term planning. It defines long-term planning in higher education, considers its…

  2. Long Term TOA - M Data and Information

    Atmospheric Science Data Center

    2015-06-30

    A Long-Term TOA and Constrained Surface Radiation Budget Project A Long-Term TOA and Constrained Surface Readiation Budget Dataset Using Merged CERES, ... and apply the knowledge to existing data to develop long-term (nearly 30 years) consistent and calibrated data product (TOA irradiances ...

  3. Prevention of pro-depressant effect of L-arginine in the forced swim test by NG-nitro-L-arginine and [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one].

    PubMed

    Ergün, Yusuf; Ergün, Ufuk Güney Ozer

    2007-01-12

    Previous studies have shown that l-arginine, the precursor of nitric oxide, has a dual effect (antidepressant and pro-depressant) in the forced swim test. The aim of the present study was to investigate whether nitric oxide-cGMP pathway was involved in this dual effect. Porsolt swim test was conducted to resemble the symptomatology of major depressive disorder. An open field locomotor activity test was also used. L-arginine exerted a U-shape effect in the forced swim test: doses of 30, 100, 300, and 1000 mg/kg caused no alteration, statistically significant reduction, no alteration, and non-significant enhancement, respectively. Neither N(G)-nitro-L-arginine (NNA) nor [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] (ODQ) at doses of 3 mg/kg was found to be effective in the forced swim test, whereas 10 mg/kg ODQ significantly reduced the immobility time. In the presence of NNA, the antidepressant and pro-depressant effects of L-arginine disappeared, however, only the pro-depressant component of l-arginine effect was prevented by ODQ (3 and 10 mg/kg). Saline, the solvent of L-arginine and NNA, and dimethyl sulfoxide (15% in saline), the solvent of ODQ, had no effect on the duration of immobility. None of the drugs or solvents used in the present study had any effect on locomotor activity over the dose range applied. The results show that L-arginine exerts its paradoxical effects by producing nitric oxide and that cGMP seems to have a role only in the pro-depressant component.

  4. Prophylactic Administration of Silybin Ameliorates L-Arginine-Induced Acute Pancreatitis

    PubMed Central

    Uçmak, Feyzullah; Ekin, Nazım; İbiloğlu, İbrahim; Arslan, Serkan; Kaplan, İbrahim; Şenateş, Ebubekir

    2016-01-01

    Background Oxidative stress have been shown to play a role in the pathogenesis of acute pancreatitis. The aim of this study was to investigate the potential effect of silybin, a potent antioxidant, on L-arginine-induced acute pancreatitis in an experimental rat model. Material/Methods Forty female Wistar Albino rats were divided into 5 groups as follows: Group 1 (C): control group (n=8), Group 2 (SL): silybin group (n=8), Group 3 (LA): acute pancreatitis group (n=8), Group 4 (SLLA): prophylaxis group (n=8), and Group 5 (LASL): treatment group (n=8). Group C (control) received 2 intraperitoneal (i.p.) injections of physiological saline at an interval of 1 h. Group SL received only a single i.p. injection of silybin. The SLLA group received a single i.p. injection of silybin before the induction of acute pancreatitis with L-arginine, whereas the LASL group received the same injection after the induction of acute pancreatitis with L-arginine. Pancreatic tissues were histopathologically examined. Levels of amylase and oxidative stress markers (total oxidant status and total anti-oxidant status) were determined in the blood samples. Oxidative stress index was calculated. Results In comparison to the LA, the prophylaxis and treatment groups showed significant improvements in serum oxidative stress parameters (p=0.001 and p=0.005, respectively). Histopathological analysis showed that the treatment group had significant improvements in edema scores only (p=0.006), whereas the prophylaxis group had the same improvements in inflammation and necrosis scores as well as in total scores (p=0.004, 0.006, and 0.004, respectively). Conclusions When used for prophylactic rather than therapeutic purposes, silybin ameliorates serum oxidative stress parameters and improves histopathological results via its antioxidant and anti-inflammatory properties. PMID:27725627

  5. NO accounts completely for the oxygenated nitrogen species generated by enzymic L-arginine oxygenation.

    PubMed Central

    Mülsch, A; Vanin, A; Mordvintcev, P; Hauschildt, S; Busse, R

    1992-01-01

    We have assessed the stoichiometry of the nitric oxide (NO) synthase reaction by using a novel e.p.r. technique. NO generated by crude and partially purified NO synthase from endothelial cells and Escherichia coli-lipopolysaccharide-activated macrophages was trapped by a ferrous diethyldithiocarbamate complex dispersed in yeast. The paramagnetic ferrous mononitrosyl dithiocarbamate complex formed exhibited a characteristic e.p.r. signal at g perpendicular = 2.035 and g parallel = 2.02 with a triplet hyperfine structure (hfs) at g perpendicular. NO, 3-morpholinosydnonimine and S-nitroso-L-cysteine, but not nitrite or hydroxylamine, generated a similar e.p.r. signal. NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine. Incubation with [15N]NG-L-arginine caused an e.p.r. signal with doublet hfs, indicating that the nitrosyl nitrogen derived exclusively from the guanidino nitrogen. The amount of NO generated by NO synthase as measured by e.p.r. technique was compared with formation of L-[3H]citrulline from L-[3H]arginine. NO and L-citrulline were detected at a 1:1 ratio with both NO synthase preparations. GSH and thiol depletion did not significantly affect NO synthase activity, excluding S-nitrosothiols as intermediates in the NO synthase reaction. We conclude that NO fully accounts for the immediate oxygenated nitrogen species derived from the enzymic oxygenation of L-arginine. PMID:1281408

  6. The Effects of L-arginine on the Hippocampus of Male Rat Fetuses under Maternal Stress

    PubMed Central

    Mahmoudi, Reza; Enant, Elham; Delaviz, Hamdollah; Rad, Parastou; Roozbehi, Amrollah; Jafari Barmak, Mehrzad; Azizi, Arsalan

    2016-01-01

    Introduction: Prenatal stress has deleterious effects on the development of the brain and is associated with behavioral and psychosocial problems in childhood and adulthood. This study aimed to determine the protective effect of L-arginine on fetal brain under maternal stress. Methods: Twenty pregnant Wistar rats (weighting 200–230 g) were randomly divided into 4 groups (n=5 for each group). The first nonstress and stress groups received 2 mL of normal saline and the other nonstress and stress two groups received L-arginine (200 mg/kg, IP) from their 5th to 20th days of pregnancy. The pregnant rats were killed on 20th day and the brain fetuses removed and prefrontal cortical thickness, total neurons in the prefrontal cortex and in the areas of CA1, CA2, and CA3 of the hippocampus were measured and counted. Nitrite levels in the brain were measured as an indicator for nitric oxide (NO) level. Results: There was a significant decrease of mean number of pyramidal cells in the CA1 in prenatal stress group compared to nonstress and nonstress plus arginine groups. The NO level in brain tissue increased significantly in the stress plus arginine (3.8±0.4 nmol/mg) and in nonstress rats (2.9±0.3 nmol/mg) compared to the stress group (1.8±0.1 nmol/mg). Prefrontal cortical thickness decreased significantly in stress rats (1.2±0.09 mm) compared to the nonstress plus arginine (1.7±0.15 mm) and nonstress (1.6±0.13 mm) groups. Discussion: Results indicated that prenatal stress could lead to neurodegeneration of hippocampus and prefrontal cortex of rat fetuses. L-arginine as a precursor of NO synthesis had neuroprotective effect during prenatal stress and could be used an effective treatment for stress. PMID:27303594

  7. X-ray radiation of poly-L-arginine hydrochloride and multilayered DNA-coatings

    NASA Astrophysics Data System (ADS)

    Stypczyńska, Agnieszka; Nixon, Tony; Mason, Nigel

    2014-11-01

    The aim of this work was to determine the chemical changes induced in thin films of the dry polypeptide poly-L-arginine hydrochloride and its mixture with calf thymus deoxyribonucleic acid (DNA) during 5 h of soft X-ray exposure. The physical and chemical effects of the soft X-ray irradiation were studied using X-ray Photoelectron Spectroscopy (XPS). Analysis of O1 s, N1 s and C1 s features in XPS spectra reveals the existence of several routes of radiation-induced decomposition and shows quantitative and qualitative changes.

  8. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  9. Histological and immunohistochemical effects of L-arginine and silymarin on TNBS-induced inflammatory bowel disease in rats.

    PubMed

    Al-Drees, Abdul; Khalil, Mahmoud Salah

    2016-11-01

    Inflammatory bowel disease (IBD) is a chronic disease that affects quality of life. Various mediators are involved in IBD pathogenesis including inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), cytochrome c, heat shock protein 70 (HSP70) and tumor necrosis factor (TNF)-α. L-Arginine (L-Arg) can be depleted in IBD, and silymarin inhibits neutrophil infiltration, NF-κB, and TNF-α, which have crucial roles in inducing IBD. This study aimed to investigate whether silymarin and L-Arg supplementation decreases IBD progression in trinitrobenzine-sulfonic acid (TNBS)-induced colitis. Fifty adult male albino rats were randomized into five groups (10 animals per group): Group I rats orally received 100 mg silymarin/kg body weight once daily; Group II rats orally received 2 mg L-Arg/100 g body weight in 5 mL distilled water once daily; Group III rats rectally received 0.85 mL TNBS in 50% ethanol to induce colitis; Group IV rats were treated similar to group III and, on recovery from anesthesia, received silymarin as described for group I; and Group V rats were treated similar to group III and, on recovery from anesthesia, received L-Arg as described for group II. On day 7, the rats were anesthetized, and blood samples were collected to determine the serum concentrations of TNF-α. Laparotomy and total colectomy were performed for macroscopic, histological, and immunohistochemical investigations. The results showed that silymarin and L-Arg macroscopically and microscopically ameliorated TNBS-induced colitis; significantly decreased the serum levels of TNF-α; inhibited the colonic expression of iNOS, NF-κB, and cytochrome c; and increased expression of HSP70. Our results suggest that these complementary medicines could be used to supplement current treatments for IBD.

  10. Effects of L-arginine on solubilization and purification of plant membrane proteins.

    PubMed

    Arakawa, Junji; Uegaki, Masamichi; Ishimizu, Takeshi

    2011-11-01

    Biochemical analysis of membrane proteins is problematic at the level of solubilization and/or purification because of their hydrophobic nature. Here, we developed methods for efficient solubilization and purification of membrane proteins using L-arginine. The addition of 100 mM of basic amino acids (L-arginine, L-lysine, and L-ornithine) to a detergent-containing solubilization buffer enhanced solubilization (by 2.6-4.3 fold) of a model membrane protein-polygalacturonic acid synthase. Of all the amino acids, arginine was the most effective additive for solubilization of this membrane protein. Arginine addition also resulted in the best solubilization of other plant membrane proteins. Next, we examined the effects of arginine on purification of a model membrane protein. In anion-exchange chromatography, the addition of arginine to the loading and elution buffers resulted in a greater recovery of a membrane protein. In ultrafiltration, the addition of arginine to a protein solution significantly improved the recovery of a membrane protein. These results were thought to be due to the properties of arginine that prevent aggregation of hydrophobic proteins. Taken together, the results of our study showed that arginine is useful for solubilization and purification of aggregate-prone membrane proteins.

  11. Role of L-arginine in the biological effects of blue light

    NASA Astrophysics Data System (ADS)

    Makela, Anu M.

    2005-11-01

    Arginine, a semi-essential amino acid, and metabolites of arginine exert multiple biological effects. It has been known that arginine causes the release of various hormones such as insulin, glucagon, growth hormone, prolactin, and adrenal catecholamines. Arginine infusion also produces vasodilation, and in the kidney increased plasma flow accompanied by increases in glomerular filtration rate (GFR). Recent studies have showed that blue and red light irradiation in vitro and in vivo can increase production of nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS). These then can modulate the production and secretion of several cytokines and other mediators and play an important role as regulatory mediators in signaling processes which can then modulate the production, mobilization and homing of stem cells. It is proposed that some of the therapeutic effects of light can be considered to be due to the changes in the metabolism of L-arginine. The regulation of L-arginine turnover by the use of light at blue wavelengths between 400nm and 510nm can be the explanation for some of the observed effects of blue light: lowering of blood pressure, pain killing effect, regulating insulin production, anti-inflammatory action, and possible effects on the release and homing of stem cells.

  12. Involvement of thrombopoietin in acinar cell necrosis in L-arginine-induced acute pancreatitis in mice.

    PubMed

    Shen, Jiaqing; Wan, Rong; Hu, Guoyong; Wang, Feng; Shen, Jie; Wang, Xingpeng

    2012-10-01

    Thrombopoietin (TPO) plays an important role in injuries of different tissues. However, the role of TPO in acute pancreatitis (AP) is not yet known. The aim of the study was to determine the involvement of TPO in AP. Serum TPO was assayed in necrotizing pancreatitis induced by L-arginine in mice. Recombinant TPO and anti-TPO antibody were given to mice with necrotizing pancreatitis. Amylase, lipase, lactate dehydrogenase, myeloperoxidase activity and pancreatic water content were assayed in serum and tissue samples. Pancreas and lung tissue samples were also collected for histological evaluation. Immunohistochemistry of amylase α and PCNA were applied for the study of acinar regeneration and TUNEL assay for the detection of apoptosis in the pancreas. Increased levels of serum TPO were found in necrotizing pancreatitis. After TPO administration, more severe acinar necrosis was found and blockade of TPO reduced the acinar necrosis in this AP model. Acinar regeneration and apoptosis in the pancreas were affected by TPO and antibody treatment in necrotizing pancreatitis. The severity of pancreatitis-associated lung injury was worsened after TPO treatment, but attenuated after Anti-TPO antibody treatment. In conclusion, serum TPO is up-regulated in the necrotizing pancreatitis induced by L-arginine in mice and may be a risk factor for the pancreatic acinar necrosis in AP. As a pro-necrotic factor, blockade of TPO can attenuate the acinar necrosis in AP and may be a possible therapeutic intervention for AP.

  13. Long-Term Mortality Trends

    Cancer.gov

    This infographic shows the National Cancer Institute 10-year Mortality Trends. The graphs show the Average Annual Percent of Change (AAPC) 2002-2011. For Men, Liver & IBD: 2.6*, Soft Tissue inc. Heart: 0.8*, Pancreas: 0.3*, Melanoma: 0.3*, Bladder: 0, Brain & ONS: -0.4, Oral Cavity: -0.5, Esophagus: -0.5*, Kidney: -0.8*, Leukemia: -0.9*, Myeloma: -1.1*, All Sites: -1.8*, Non Hodgkin Lymphoma: -2.3*, Larynx: -2.5*, Lung and Bronchus: -2.6*, Colon and Rectum: -3.9*, Stomach: -3.1*, and Prostate: -3.3*. For Women, Liver & IBD: 1.9*, Corpus & Uterus: 1.0*, Pancreas: 0.4*, Bladder: -0.4*, Kidney: -0.9*, Brain & ONS: -0.9*, Leukemia: -1.1*, Gallbladder: -1.2*, Lung & Bronchus: -1.2*, Cervix: -1.3*, All Sites: -1.4*, Esophagus: -1.5*, Myeloma: -1.6*, Breast: -1.9*, Oral Cavity: -2.0*, Ovary: -2.0*, Stomach: -2.7*, Colon & Rectum: -2.9*, and Non-Hodgkin Lymphoma: -3.1*. * AAPC is significantly different from zero (p<.05). www.cancer.gov Source: Special section of the Annual Report to the Nation on the Status of Cancer, 1975-2011

  14. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

    PubMed Central

    Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine

  15. Breeding L-arginine-producing strains by a novel mutagenesis method: Atmospheric and room temperature plasma (ARTP).

    PubMed

    Cheng, Gong; Xu, Jianzhong; Xia, Xiuhua; Guo, Yanfeng; Xu, Kai; Su, Cunsheng; Zhang, Weiguo

    2016-07-03

    A plasma jet, driven by an active helium atom supplied with an atmospheric and room temperature plasma (ARTP) biological breeding system, was used as a novel method to breed L-arginine high-yielding strains. A mutant with resistance to L-homoarginine and 8-azaguaine, ARG 3-15 (L-HA(r), 8-AG(r), L-His(-)), was screened after several rounds of screening. The L-arginine production of these mutants was more than that of the original strain, increased by 43.79% for ARG 3-15. Moreover, N-acetyl-L-glutamate synthase activity of these mutants was also increased. After a series of passages, the hereditary properties of these mutants were found to be stable. Interestingly, beet molasses was utilized in a co-feeding fermentation and benefited to increase the productivity by 5.88%. Moreover, the fermentation with 1.0 g/L betaine could produce 9.33% more L-arginine than without betaine. In fed-batch fermentation, C. glutamicum ARG 3-15 began to produce L-arginine at the initial of logarithmic phase, and continuously increased over 24 hr to a final titer of 45.36 ± 0.42 g/L. The L-arginine productivity was 0.571 g/L/hr and the conversion of glucose (α) was 32.4% after 96 hr. These results indicated that C. glutamicum ARG 3-15 is a promising industrial producer.

  16. Supplementation of bovine embryo culture medium with L-arginine improves embryo quality via nitric oxide production.

    PubMed

    Santana, Priscila Di Paula Bessa; Silva, Thiago Velasco Guimarães; da Costa, Nathália Nogueira; da Silva, Bruno Barauna; Carter, Timothy Frederick; Cordeiro, Marcela da Silva; da Silva, Bruno José Martins; Santos, Simone do Socorro Damasceno; Herculano, Anderson Manoel; Adona, Paulo Roberto; Ohashi, Otávio Mitio; Miranda, Moysés dos Santos

    2014-10-01

    Nitric oxide (NO) is a cell-signaling molecule that regulates a variety of molecular pathways. We investigated the role of NO during preimplantation embryonic development by blocking its production with an inhibitor or supplementing in vitro bovine embryo cultures with its natural precursor, L-arginine, over different periods. Endpoints evaluated included blastocyst rates, development kinetics, and embryo quality. Supplementation with the NO synthase inhibitor N-Nitro-L-arginine-methyl ester (L-NAME) from Days 1 to 8 of culture decreased blastocyst (P < 0.05) and hatching (P < 0.05) rates. When added from Days 1 to 8, 50 mM L-arginine decreased blastocyst rates (P < 0.001); in contrast, when added from Days 5 to 8, 1 mM L-arginine improved embryo hatching rates (P < 0.05) and quality (P < 0.05) as well as increased POU5F1 gene expression (P < 0.05) as compared to the untreated control. Moreover, NO levels in the medium during this culture period positively correlated with the increased embryo hatching rates and quality (P < 0.05). These data suggest exerts its positive effects during the transition from morula to blastocyst stage, and that supplementing the embryo culture medium with L-arginine favors preimplantation development of bovine embryos.

  17. Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet

    PubMed Central

    Miczke, Anna; Suliburska, Joanna; Pupek-Musialik, Danuta; Ostrowska, Lucyna; Jabłecka, Anna; Krejpcio, Zbigniew; Skrypnik, Damian; Bogdański, Paweł

    2015-01-01

    Object: The purpose of this study was to determine whether supplementation with L-arginine, a substrate used in the production of nitric oxide, had an effect on adiponectin concentration in rats fed a high-fat diet. The influence of L-arginine on insulin resistance was also evaluated. Materials and methods: The experiment was performed using 36 Wistar rats divided into three groups: group 1 was fed a standard diet, group 2 a high-fat (HF) diet, group 3 a HF diet supplemented with L-arginine. After 42 days, serum levels of lipids, glucose, insulin, NO, and adiponectin were measured. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment (HOMA). Results: Body mass was equal in all 3 groups, at the beginning as well as at the end of the study, however, in group 2 the amount of visceral fat was greater after 42 days. In group 3, there was a tendency for visceral fat to decrease. An increase in cholesterol, triglycerides, insulin and HOMA-IR, as well as a decrease in NO and adiponectin were seen in group 2, while in group 3, L-arginine supplementation ameliorated these disturbances. Conclusions: Our study shows that L-arginine supplementation in rats fed a HF diet is associated with an increase in insulin sensitivity. Our findings suggest that the underlying mechanism could be at least partially related to an increase in adiponectin concentration. PMID:26379826

  18. Long-term solar-terrestrial observations

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The results of an 18-month study of the requirements for long-term monitoring and archiving of solar-terrestrial data is presented. The value of long-term solar-terrestrial observations is discussed together with parameters, associated measurements, and observational problem areas in each of the solar-terrestrial links (the sun, the interplanetary medium, the magnetosphere, and the thermosphere-ionosphere). Some recommendations are offered for coordinated planning for long-term solar-terrestrial observations.

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

    PubMed

    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.

  20. Genome-wide association reveals that common genetic variation in the kallikrein-kinin system is associated with serum L-arginine levels.

    PubMed

    Zhang, Weihua; Jernerén, Fredrik; Lehne, Benjamin C; Chen, Ming-Huei; Luben, Robert N; Johnston, Carole; Elshorbagy, Amany; Eppinga, Ruben N; Scott, William R; Adeyeye, Elizabeth; Scott, James; Böger, Rainer H; Khaw, Kay-Tee; van der Harst, Pim; Wareham, Nicholas J; Vasan, Ramachandran S; Chambers, John C; Refsum, Helga; Kooner, Jaspal S

    2016-11-30

    L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 µmol/l per allele copy, p=1×10(-24)), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 µmol/l per allele copy, p=7×10(-12)). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements (p<0.004). The two sentinel SNPs are in nearly complete LD with the nonsynonymous SNP rs3733402 at KLKB1 and the 5'-UTR SNP rs1801020 at F12, respectively. SNPs at both loci are associated with blood pressure. Our findings provide new insight into the genetic regulation of L-arginine and its potential relationship with cardiovascular risk.

  1. Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum.

    PubMed

    Lubitz, Dorit; Jorge, João M P; Pérez-García, Fernando; Taniguchi, Hironori; Wendisch, Volker F

    2016-10-01

    L-arginine is a semi-essential amino acid with application in cosmetic, pharmaceutical, and food industries. Metabolic engineering strategies have been applied for overproduction of L-arginine by Corynebacterium glutamicum. LysE was the only known L-arginine exporter of this bacterium. However, an L-arginine-producing strain carrying a deletion of lysE still accumulated about 10 mM L-arginine in the growth medium. Overexpression of the putative putrescine and cadaverine export permease gene cgmA was shown to compensate for the lack of lysE with regard to L-arginine export. Moreover, plasmid-borne overexpression of cgmA rescued the toxic effect caused by feeding of the dipeptide Arg-Ala to lysE-deficient C. glutamicum and argO-deficient Escherichia coli strains. Deletion of the repressor gene cgmR improved L-arginine titers by 5 %. Production of L-lysine and L-citrulline was not affected by cgmA overexpression. Taken together, CgmA may function as an export system not only for the diamine putrescine and cadaverine but also for L-arginine. The major export system for L-lysine and L-arginine LysE may also play a role in L-citrulline export since production of L-citrulline was reduced when lysE was deleted and improved by 45 % when lysE was overproduced.

  2. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

    PubMed

    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 N(G) -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 according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic 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.

  3. Recovery of Endothelial Function in Severe Falciparum Malaria: Relationship with Improvement in Plasma L-Arginine and Blood Lactate Concentrations

    PubMed Central

    Yeo, Tsin W.; Lampah, Daniel A.; Gitawati, Retno; Tjitra, Emiliana; Kenangalem, Enny; McNeil, Yvette R.; Darcy, Christabelle J.; Granger, Donald L.; Weinberg, J. Brice; Lopansri, Bert K.; Price, Ric N.; Duffull, Stephen B.; Celermajer, David S.; Anstey, Nicholas M.

    2009-01-01

    Background Severe malaria is characterized by microvascular obstruction, endothelial dysfunction, and reduced levels of L-arginine and nitric oxide (NO). L-Arginine infusion improves endothelial function in moderately severe malaria. Neither the longitudinal course of endothelial dysfunction nor factors associated with recovery have been characterized in severe malaria. Methods Endothelial function was measured longitudinally in adults with severe malaria (n = 49) or moderately severe malaria (n = 48) in Indonesia, using reactive hyperemia peripheral arterial tonometry (RH-PAT). In a mixed-effects model, changes in RH-PAT index values in patients with severe malaria were related to changes in parasitemia, lactate, acidosis, and plasma L-arginine concentrations. Results Among patients with severe malaria, the proportion with endothelial dysfunction fell from 94% (46/49 patients) to 14% (6/42 patients) before discharge or death (P <.001). In severe malaria, the median time to normal endothelial function was 49 h (interquartile range, 20–70 h) after the start of antimalarial therapy. The mean increase in L-arginine concentrations in patients with severe malaria was 11 μmol/L/24 h (95% confidence interval [CI], 9–13 μmol/L/24 h), from a baseline of 49 μmol/L (95% CI, 37–45 μmol/L). Improvement of endothelial function in patients with severe malaria correlated with increasing levels of L-arginine (r = 0.56; P =.008) and decreasing levels of lactate (r = −0.44; P =.001). Conclusions Recovery of endothelial function in severe malaria is associated with recovery from hypoargininemia and lactic acidosis. Agents that can improve endothelial NO production and endothelial function, such as L-arginine, may have potential as adjunctive therapy early during the course of severe malaria. PMID:18605903

  4. NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide.

    PubMed Central

    Kilbourn, R G; Gross, S S; Jubran, A; Adams, J; Griffith, O W; Levi, R; Lodato, R F

    1990-01-01

    Clinical assessment of the activity of tumor necrosis factor (TNF) against human cancer has been limited by a dose-dependent cardiovascular toxicity, most frequently hypotension. TNF is also thought to mediate the vascular collapse resulting from bacterial endotoxin. The present studies address the mechanism by which TNF causes hypotension and provide evidence for elevated production of nitric oxide, a potent vasodilator initially characterized as endothelium-derived relaxing factor. Nitric oxide is synthesized by several cell types, including endothelial cells and macrophages, from the guanidino nitrogen of L-arginine; the enzymatic pathway is competitively inhibited by NG-methyl-L-arginine. We found that hypotension induced in pentobarbital-anesthetized dogs by TNF (10 micrograms/kg, i.v., resulting in a fall in mean systemic arterial pressure from 124.7 +/- 7 to 62.0 +/- 22.9 mmHg; 1 mmHg = 133 Pa) was completely reversed within 2 min following administration of NG-methyl-L-arginine (4.4 mg/kg, i.v.). In contrast, NG-methyl-L-arginine failed to reverse the hypotensive response to an equivalent depressor dose of nitroglycerin, a compound that acts by forming nitric oxide by a nonenzymatic, arginine-independent mechanism. The effect of NG-methyl-L-arginine on TNF-induced hypotension was antagonized, and the hypotension restored, by administration of excess L-arginine (100 mg/kg, i.v.). Our findings suggest that excessive nitric oxide production mediates the hypotensive effect of TNF. PMID:2333306

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

    PubMed

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

    2010-01-01

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

  6. Bioanalytical profile of the L-arginine/nitric oxide pathway and its evaluation by capillary electrophoresis◇

    PubMed Central

    Boudko, Dmitri Y.

    2007-01-01

    This review briefly summarizes recent progress in fundamental understanding and analytical profiling of the L-arginine/nitric oxide (NO) pathway. It focuses on key analytical references of NO actions and on the experimental acquisition of these references in vivo, with capillary electrophoresis (CE) and high-performance capillary electrophoresis (HPCE) comprising one of the most flexible and technologically promising analytical platform for comprehensive high-resolution profiling of NO-related metabolites. Second aim of this review is to express demands and bridge efforts of experimental biologists, medical professionals and chemical analysis-oriented scientists who strive to understand evolution and physiological roles of NO and to develop analytical methods for use in biology and medicine. PMID:17329176

  7. Ground based experiments on the growth and characterization of L-Arginine Phosphate (LAP) crystals

    NASA Technical Reports Server (NTRS)

    Rao, S. M.; Cao, C.; Batra, A. K.; Lal, R. B.; Mookherji, T. K.

    1991-01-01

    L-Arginine Phosphate (LAP) is a new nonlinear optical material with higher efficiency for harmonic generation compared to KDP. Crystals of LAP were grown in the laboratory from supersaturated solutions by temperature lowering technique. Investigations revealed the presence of large dislocation densities inside the crystals which are observed to produce refractive index changes causing damage at high laser powers. This is a result of the convection during crystal growth from supersaturated solutions. It is proposed to grow these crystals in a diffusion controlled growth condition under microgravity environment and compare the crystals grown in space with those grown on ground. Physical properties of the solutions needed for modelling of crystal growth are also presented.

  8. Effects of l-arginine on the physicochemical and gel properties of chicken actomyosin.

    PubMed

    Lei, Zhen; Fu, Yuan; Xu, Peng; Zheng, Yadong; Zhou, Cunliu

    2016-11-01

    The objective of this study is to investigate the effects of l-arginine (Arg) on the physicochemical and gel properties of chicken actomyosin. The results showed that Arg increased the content of surface hydrophobicity and reactive sulfhydryl group of chicken actomyosin, but decreased storage modulus (G0). Also, Arg enhanced the first thermal transition temperature (TM1) but decreased the second thermal transition temperature (TM2). The addition of Arg favored to form a dense and uniform gel with the increased water holding capacity (WHC), strength and transverse relaxation time (T2). These results suggested that Arg may result in the formation of a uniform and continuous gel by changing the structural and thermal behavior of actomyosin in turn, ultimately contributing to the elevated WHC and strength. The results may provide new insight into the effects of Arg on the WHC and texture of meat products in the previous literatures.

  9. l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in Caenorhabditis elegans

    PubMed Central

    Ma, Heran; Ma, Yudan; Zhang, Zhixian; Zhao, Ziyuan; Lin, Ran; Zhu, Jinming; Guo, Yi; Xu, Li

    2016-01-01

    The antioxidant properties of l-arginine (l-Arg) in vivo, and its effect on enhancing resistance to oxidative stress and heat stress in Caenorhabditis elegans were investigated. C. elegans, a worm model popularly used in molecular and developmental biology, was used in the present study. Here, we report that l-Arg, at a concentration of 1 mM, prolonged C. elegans life by 26.98% and 37.02% under oxidative and heat stress, respectively. Further experiments indicated that the longevity-extending effects of l-Arg may be exerted by its free radical scavenging capacity and the upregulation of aging-associated gene expression in worms. This work is important in the context of numerous recent studies that concluded that environment stresses are associated with an increased population death rate. PMID:27690079

  10. Virtual Models of Long-Term Care

    ERIC Educational Resources Information Center

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  11. Long Term Preservation of Digital Information.

    ERIC Educational Resources Information Center

    Lorie, Raymond A.

    The preservation of digital data for the long term presents a variety of challenges from technical to social and organizational. The technical challenge is to ensure that the information, generated today, can survive long term changes in storage media, devices, and data formats. This paper presents a novel approach to the problem. It distinguishes…

  12. Long-Term Nutrition: A Clinician's Guide to Successful Long-Term Enteral Access in Adults.

    PubMed

    Bechtold, Matthew L; Mir, Fazia A; Boumitri, Christine; Palmer, Lena B; Evans, David C; Kiraly, Laszlo N; Nguyen, Douglas L

    2016-09-22

    Long-term nutrition support requires long-term enteral access. To ensure the success of long-term enteral access, many factors need to be taken into consideration. This article represents a guide to placing and maintaining access in patients requiring long-term nutrition and addresses many of the common questions regarding long-term enteral access, such as indications, types of access, feeding after access placed, and recognition and treatment of potential complications. This guide will help the clinician establish and maintain access to maximize nutrition in patients requiring long-term nutrition.

  13. Paying for long-term care.

    PubMed Central

    Estes, C L; Bodenheimer, T

    1994-01-01

    Everyone agrees that insurance for long-term care is inadequate in the United States. Disagreement exists, however, on whether such insurance should be provided through the private or public sector. Private insurance generally uses the experience-rating principle that persons with higher risk of illness are charged higher premiums. For private insurance for long-term care, this principle creates a dilemma. Most policies will be purchased by the elderly; yet, because the elderly have a high risk of needing long-term care, only about 20% of them can afford the cost of premiums. A public-private partnership by which the government partially subsidizes private long-term-care insurance is unlikely to resolve this dilemma. Only a social insurance program for long-term care can provide universal, affordable, and equitable coverage. PMID:8128712

  14. Mechanism of inactivation of hepatitis B surface antigen by N alpha-cocoyl-L-arginine ethyl ester.

    PubMed Central

    Sugimoto, Y; Toyoshima, S

    1981-01-01

    The mechanism of N alpha-cocoyl-L-arginine ethyl ester (CAE) in the inactivation of hepatitis B surface antigen (HBsAg) was investigated. The CAE increased the density of HBsAg, and particles of the antigen were destroyed in amorphous clusters, suggesting that CAE influences the lipid components of HBsAg. The lipid components such as cholesterol and phospholipid were mostly removed from the antigen by the treatment with CAE. N alpha-Lauroyl-L-[U-14C] arginine ethyl ester (LAE), a principal component of CAE, became tightly bound to HBsAg in place of the lipid components. The binding amounts of LAE in the HBsAg-LAE complex reached 3.04 +/- 0.44 microgram/mg of protein. The formation of the complex was not influenced by the presence of CAE-related compounds such as L-arginine, L-arginine ethyl ester, and N alpha-cocoyl-L-arginine. Treatment with mercaptoethanolurea, guanidine hydrochloride, and some detergents failed to resolve appreciably the labeled LAE from the labeled complex. All attempts to reactivate the CAE-treated HBsAg and to restore it morphologically from the denatured aggregates were unsuccessful. These results indicate that CAE tightly binds to HBsAg, followed by formation of stable aggregates of the denatured HBsAg-CAE complex. Images PMID:7283411

  15. Dietary L-arginine supplementation during mouse gestation enhances reproductive performance and Vegfr2 transcription activity in the fetoplacental unit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Regarded as one of the most versatile amino acids, arginine serves as a precursor for many molecules and has been reported to improve the reproductive performance of rats and pigs. To this end, we sought to determine if dietary L-arginine alters fetoplacental vascular endothelial growth factor recep...

  16. Modulatory effects of l-arginine and soy enriched diet on bone homeostasis abnormalities in streptozotocin-induced diabetic rats.

    PubMed

    El-Maraghy, Shohda A; Mehana, Noha Ali

    2015-03-05

    Diabetes mellitus is a complex syndrome which is responsible for numerous complications affecting the whole body. Osteoporosis is regarded as one of the chronic complications of diabetes mellitus that results from reduced bone formation and increased resorption. In this context, we searched for dietary supplements that preserve diabetic bone loss. Parathyroid hormone (PTH) has been suggested as a possible mechanism affecting bone homeostasis in streptozotocin (STZ)-induced diabetic rats. The osteoprotective effects of l-arginine and soy enriched diet were also investigated. Male Wistar rats were allocated into four groups; normal control, untreated STZ-diabetic rats and STZ-diabetic rats treated with either l-arginine (10mg/kg/day) or fed soy enriched diet (200 g/kg diet) for 12 weeks. l-Arginine and soy enriched diet normalized serum PTH level and increased serum osteocalcin level; bone osteocalcin, osteoprotegerin and runt-related transcription factor2 mRNA levels compared to diabetic rats. A decrease in serum pyridinoline, C-terminal telopeptides of type I collagen, cathepsin k levels and bone cathepsin k mRNA level was observed in both treated groups. Both treatments increased serum insulin and insulin like growth factor-1 levels and decreased urinary calcium excretion. In conclusion, l-arginine and soy enriched diet are effective in prevention of osteoporosis associated with diabetes mellitus.

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

    PubMed Central

    Zandifar, Alireza; Seifabadi, Sima; Zandifar, Ehsan; Beheshti, Sajedeh Sohrabi; Aslani, Abolfazl; Javanmard, Shaghayegh Haghjooy

    2015-01-01

    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 (NOx) 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 NOx 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 NOx 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. PMID:26109968

  18. Redox function of tetrahydrobiopterin and effect of L-arginine on oxygen binding in endothelial nitric oxide synthase.

    PubMed

    Berka, Vladimir; Yeh, Hui-Chun; Gao, De; Kiran, Farheen; Tsai, Ah-Lim

    2004-10-19

    Tetrahydrobiopterin (BH(4)), not dihydrobiopterin or biopterin, is a critical element required for NO formation by nitric oxide synthase (NOS). To elucidate how BH(4) affects eNOS activity, we have investigated BH(4) redox functions in the endothelial NOS (eNOS). Redox-state changes of BH(4) in eNOS were examined by chemical quench/HPLC analysis during the autoinactivation of eNOS using oxyhemoglobin oxidation assay for NO formation at room temperature. Loss of NO formation activity linearly correlated with BH(4) oxidation, and was recovered by overnight incubation with fresh BH(4). Thus, thiol reagents commonly added to NOS enzyme preparations, such as dithiothreitol and beta-mercaptoethanol, probably preserve enzyme activity by preventing BH(4) oxidation. It has been shown that conversion of L-arginine to N-hydroxy-L-arginine in the first step of NOS catalysis requires two reducing equivalents. The first electron that reduces ferric to the ferrous heme is derived from flavin oxidation. The issue of whether BH(4) supplies the second reducing equivalent in the monooxygenation of eNOS was investigated by rapid-scan stopped-flow and rapid-freeze-quench EPR kinetic measurements. In the presence of L-arginine, oxygen binding kinetics to ferrous eNOS or to the ferrous eNOS oxygenase domain (eNOS(ox)) followed a sequential mechanism: Fe(II) <--> Fe(II)O(2) --> Fe(III) + O(2)(-). Without L-arginine, little accumulation of the Fe(II)O(2) intermediate occurred and essentially a direct optical transition from the Fe(II) form to the Fe(III) form was observed. Stabilization of the Fe(II)O(2) intermediate by L-arginine has been established convincingly. On the other hand, BH(4) did not have significant effects on the oxygen binding and decay of the oxyferrous intermediate of the eNOS or eNOS oxygenase domain. Rapid-freeze-quench EPR kinetic measurements in the presence of L-arginine showed a direct correlation between BH(4) radical formation and decay of the Fe(II)O(2

  19. Exogenous L-arginine and HDL can alter LDL and ox-LDL-mediated platelet activation: using platelet P-selectin receptor numbers.

    PubMed

    Sener, Azize; Enc, Elif; Ozsavci, Derya; Vanizor-Kural, Birgul; Yanikkaya-Demirel, Gulderen; Oba, Rabia; Uras, Fikriye; Demir, Muzaffer

    2011-01-01

    The aim of this study is to investigate the effects of exogenous L-arginine and HDL on LDL and oxidized LDL (ox-LDL)-mediated platelet activation. Adenosine diphosphate (ADP)-activated platelets have been incubated with lipoproteins with or without L-arginine. P-selectin receptor numbers per platelet have been measured by flow cytometry. After incubation with only L-arginine (without lipoproteins), platelet nitric oxide (NO) levels and P-selectin receptor numbers significantly increased compared to the controls (P < .05). After incubation with LDL or ox-LDL, receptor numbers of P-selectin significantly increased (P < .001). However, P-selectin receptor numbers in platelets treated with L-arginine + LDL or L-arginine + ox-LDL decreased compared to the levels in platelets treated with only LDL or ox-LDL (P < .01, P < .001, respectively). Addition of HDL to L-arginine + ox-LDL caused significant reduction in P-selectin receptor numbers as in the control values (P < .001).We have concluded that L-arginine causes enhanced platelet NO levels and blocks the effects of LDL or ox-LDL on platelet P-selectin receptor numbers and HDL also strengthens this effect of L-arginine.

  20. L-arginine does not improve biochemical and hormonal response in trained runners after 4 weeks of supplementation.

    PubMed

    Alvares, Thiago Silveira; Conte-Junior, Carlos Adam; Silva, Joab Trajano; Paschoalin, Vânia Margaret Flosi

    2014-01-01

    It has been hypothesized that L-arginine improves exercise performance by increasing nitric oxide synthesis and levels of insulin and growth hormone (GH). Metabolic and hormonal responses to chronic L-arginine supplementation may clarify the mechanisms underlying its putative physiologic effects on physical performance. Therefore, the aim of this study was to investigate the effects that 4 weeks of supplementation with L-arginine would have on metabolic and hormonal parameters at rest and in response to exercise. Fifteen healthy runners were divided into treatment (ARG; 6 g L-arginine) and placebo (PLA; 6 g cornstarch) groups. On the first visit, blood samples were collected for baseline, and the supplement or placebo was provided. After 4 weeks of supplementation (second visit), blood samples were collected at the following intervals: at rest, immediately after the first 5-km time-trial running test (5km-TT), immediately after the second 5km-TT, and after 20 minutes of recovery (+20). In addition to exercise performance (total running time), plasma nitrate, nitrite, nitrate plus nitrite, cyclic guanosine monophosphate, lactate, ammonia and serum insulin, GH, insulin-like growth factor 1, and cortisol concentrations were evaluated. There were significant increases in plasma nitrite, cyclic guanosine monophosphate, lactate, ammonia and serum GH, and cortisol at the first 5km-TT, immediately after the second 5km-TT, and +20 in both ARG and PLA. Nitrate plus nitrite and nitrate increased only at +20. No significant change was observed in serum insulin and insulin-like growth factor 1 in any sample period. Total running time did not differ significantly between the 2 tests, in either ARG or PLA. Thus, according to our results, 4 weeks of L-arginine supplementation did not cause beneficial changes in metabolic and hormonal parameters, beyond those achieved with exercise alone.

  1. Effects of acute supplementation of L-arginine and nitrate on endurance and sprint performance in elite athletes.

    PubMed

    Sandbakk, Silvana Bucher; Sandbakk, Øyvind; Peacock, Oliver; James, Philip; Welde, Boye; Stokes, Keith; Böhlke, Nikolai; Tjønna, Arnt Erik

    2015-08-01

    This study examined the effects of acute supplementation with L-arginine and nitrate on running economy, endurance and sprint performance in endurance-trained athletes. In a randomised cross-over, double-blinded design we compared the effects of combined supplementation with 6 g L-arginine and 614 mg nitrate against 614 mg nitrate alone and placebo in nine male elite cross-country skiers (age 18 ± 0 years, VO2max 69.3 ± 5.8 ml ⋅ min(-1) ⋅ kg(-1)). After a 48-hour standardisation of nutrition and exercise the athletes were tested for plasma nitrate and nitrite concentrations, blood pressure, submaximal running economy at 10 km ⋅ h(-1) and 14 km ⋅ h(-1) at 1% incline and 180 m as well as 5-km time-trial running performances. Plasma nitrite concentration following L-arginine + nitrate supplementation (319 ± 54 nmol ⋅ L(-1)) did not differ from nitrate alone (328 ± 107 nmol ⋅ L(-1)), and both were higher than placebo (149 ± 64 nmol ⋅ L(-1), p < 0.01). There were no differences in physiological responses during submaximal running or in 5-km performance between treatments. The plasma nitrite concentrations indicate greater nitric oxide availability both following acute supplementation of L-arginine + nitrate and with nitrate alone compared to placebo, but no additional effect was revealed when L-arginine was added to nitrate. Still, there were no effects of supplementation on exercise economy or endurance running performance in endurance-trained cross-country skiers.

  2. Roadmap to Long-Term Monitoring Optimization

    EPA Pesticide Factsheets

    This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...

  3. Mental Health in Long Term Care Settings.

    ERIC Educational Resources Information Center

    Shore, Herbert

    1978-01-01

    There are many ways in which long-term care facilities attempt to cope with the mental health problems of the elderly. The author reviews five factors crucial to effective care for the aged in these facilities. (Author/RK)

  4. Long-term-care legal update.

    PubMed

    Fiesta, J

    1998-04-01

    As more nurses move from the acute care setting to long-term-care and home health care, different practice issues arise. To maximize liability protection, nurses must understand the legal issues unique to each delivery system.

  5. Long-Term Care Ombudsman Program

    MedlinePlus

    ... Provided to Persons Living in Long-Term Care Facilities Program data for FY 2013 indicate that long- ... least quarterly Conducted 5,417 training sessions in facilities on such topics as residents’ rights Provided 129, ...

  6. Long-Term Cyclophosphamide Treatment in a Case with Serpiginous Choroiditis.

    PubMed

    Sahin, Ozlem G

    2010-10-05

    PURPOSE: To report the effect of long-term therapy with the alkylating agent cyclophosphamide in a case with serpiginous choroiditis and thus to contribute to the previously reported few cases showing the beneficial effect of long-term cyclophosphamide therapy for serpiginous choroiditis. PROCEDURES: Oral cyclophosphamide therapy for 12 months in a case with unilateral active serpiginous choroiditis. RESULTS: The active lesion responded well to long-term therapy with cyclophosphamide without recurrences and significant systemic side-effects. CONCLUSIONS: Long-term therapy with cyclophosphamide for serpiginous choroiditis is effective for improving vision and preventing recurrences.

  7. The 2014 Long-Term Budget Outlook

    DTIC Science & Technology

    2014-07-16

    Treasury from the Federal Reserve System, customs duties, estate and gift taxes, and miscellaneous fees and fines. Actual Extended Baseline...Office’s (CBO’s) most recent analysis of the outlook for the federal budget over the long term. My statement today summarizes The 2014 Long-Term Budget...Outlook, which was released yesterday.1 Between 2009 and 2012, the federal government recorded the largest budget deficits relative to the size of

  8. Evidence-based long term care design.

    PubMed

    Calkins, Margaret P

    2009-01-01

    Research on the impact of the built environment in long-term care settings continues to grow. This article focuses on work conducted and published since 2000, when an earlier review on research on dementia and design was published. The vast majority of research that addressed neurological conditions in residents in long-term care settings (assisted living and nursing homes) relates to Alzheimer's disease and related dementias.

  9. Long Term Outcomes after Pediatric Liver Transplantation

    PubMed Central

    2013-01-01

    Long term outcomes after liver transplantation are major determinants of quality of life and of the value of this heroic treatment. As short term outcomes are excellent, our community is turning to take a harder look at long term outcomes. The purpose of this paper is to review these outcomes, and highlight proposed treatments, as well as pressing topics needing to be studied. A systemic review of the English literature was carried in PubMed, covering all papers addressing long term outcomes in pediatric liver transplant from 2000-2013. Late outcomes after pediatric liver transplant affect the liver graft in the form of chronic liver dysfunction. The causes include rejection particularly humoral rejection, but also de novo autoimmune hepatitis, and recurrent disease. The metabolic syndrome is a major factor in long term cardiovascular complication risk. Secondary infections, kidney dysfunction and malignancy remain a reality of those patients. There is growing evidence of late cognitive and executive function delays affecting daily life productivity as well as likely adherence. Finally, despite a good health status, quality of life measures are comparable to those of children with chronic diseases. Long term outcomes are the new frontier in pediatric liver transplantation. Much is needed to improve graft survival, but also to avoid systemic morbidities from long term immunosuppression. Quality of life is a new inclusive measure that will require interventions and innovative approaches respectful not only on the patients but also of their social circle. PMID:24511516

  10. Cardio-protective effects of combined l-arginine and insulin: Mechanism and therapeutic actions in myocardial ischemia-reperfusion injury.

    PubMed

    Venardos, Kylie M; Rajapakse, Niwanthi W; Williams, David; Hoe, Louise S; Peart, Jason N; Kaye, David M

    2015-12-15

    Reduced nitric oxide (NO) bioavailability plays a central role in the pathogenesis of myocardial ischemia-reperfusion injury (I-R), and reduced l-arginine transport via cationic amino acid transporter-1 is a key contributor to the reduced NO levels. Insulin can increase NO levels by increasing the transport of its substrate l-arginine but insulin alone exerts minimal cardiac protection in I-R. We hypothesized that combined insulin and l-arginine may provide cardioprotective effects in the setting of myocardial I-R. The effect of supplemental insulin, l-arginine and the combination was examined in cardiomyocytes exposed to hypoxia/reoxygenation and in isolated perfused mouse hearts undergoing ischemia/reperfusion. When compared to controls, cardiomyocytes treated upon reoxygenation with 1nM insulin+1mM l-arginine exhibited significant (all P<0.05) improvements in NO generation and mitochondrial membrane potential, with a concomitant fall in reactive oxygen species production and LDH release. Insulin also increased l-arginine uptake following hypoxia-reoxygenation (P<0.05; n=4-6). In langendorff perfused isolated mouse hearts, combined l-arginine-insulin treatment upon reperfusion significantly (all P<0.05; n=9-11) improved recovery of left ventricular developed pressure, rate pressure product and end diastolic pressure following ischemia, independent of any changes in post-ischemic coronary flow, together with significantly lower LDH release. The observed improvements were greater than l-arginine or insulin treatment alone. In isolated cardiomyocytes (n=3-5), 1nM insulin caused cationic amino acid transporter-1 to redistribute to the cellular membrane from the cytosol and the effects of insulin on l-arginine uptake were partially dependent on the PI3K/Akt pathway. l-arginine-insulin treatment may be a novel strategy to ameliorate I-R injury.

  11. Intrathecal L-arginine reduces the antinociception of sevoflurane in formalin-induced pain in rats.

    PubMed

    Chen, Jian-Qing; Zeng, Yin-Ming; Dai, Ti-Jun; Tang, Qi-Feng

    2015-03-17

    The purpose of this study was to investigate the contribution of spinal nitric oxide (NO) to the antinociceptive effects of emulsified sevoflurane in rats. Formalin tests were used to assess the nociceptive response. Immunohistochemistry was performed to determine the effects of emulsified sevoflurane on formalin-induced changes of Fos-like immunoreactive (Fos-LI)-positive neurons in the spinal cord. We found that emulsified sevoflurane administered intraperitoneally at a dosage of 2.5 ml/kg did not impair motor performance in rats, but it significantly decreased the formalin-induced paw licking time. Furthermore, Fos-LI-positive neurons were mainly found in the ipsilateral dorsal horn after the injection of formalin. The administration of emulsified sevoflurane significantly decreased Fos-LI-labeled neurons. Finally, intrathecal L-arginine alone did not affect the basal pain threshold, but it significantly decreased the antinociceptive response of emulsified sevoflurane against formalin injection and the suppressive effects of sevoflurane on formalin-induced Fos protein expression (P<0.05). These data suggest that spinal cord NO is involved in the antinociception of sevoflurane in rats.

  12. Improved blood compatibility of poly(ethylene terephthalate) films modified with L-arginine.

    PubMed

    Liu, Yun; Chen, Jie-Rong; Yang, Yun; Wu, Feng

    2008-01-01

    In order to improve the blood compatibility of the commonly used blood-contacting biomaterial poly(ethylene terephthalate) (PET), in this study PET films were chemically modified with L-arginine (L-Arg) by a three-step-procedure using glutaraldehyde (GA) as a cross-linker. The composition and chemical structure of PET and its change with surface modification were examined by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy, while the change in hydrophilicity was judged by water contact angles measurement. The result of water contact measurement indicated that the modified films became more hydrophilic than PET with the contact angle decreasing from 78.5 degrees for PET to 43.7 degrees for PET-Arg. The protein adsorption on the film surface was evaluated by bicinchoninic acid assay (BCA) method, and the result showed that the L-Arg-modified films decreased the amount of protein adsorption by about 25%. The in vitro blood compatibility such as platelet adhesion (observed by scanning electron microscopy) and thrombus formation was also investigated, and the results demonstrated that the L-Arg-modified films significantly suppressed platelet adhesion and aggregation and reduced the thrombus formation by about 67% compared with PET.

  13. L-canavanine inhibits L-arginine uptake by broiler chicken intestinal brush border membrane vesicles.

    PubMed

    Rueda, E; Michelangeli, C; Gonzalez-Mujica, F

    2003-09-01

    1. Intestinal brush border membrane vesicles (BBMV) were prepared from 3-week-old broiler chickens. 2. Electron microscopy of the BBMV fraction showed single membrane vesicles of different sizes with no electron dense material inside. No other organelles were observed. The sucrase and maltase activities were enriched by factors of 16 and 18, respectively, in the BBMV fraction in comparison with the homogenate. On the other hand, the Na+/K+-ATPase sensitivity to ouabain was increased by a factor of 0.8. 3. The BBMV showed a maximum L-[14C]-arginine uptake (944.9 +/- 22.9 pmoles/mg protein) at 45 s and thereafter it declined slowly. In the presence of 0.5 mM L-canavanine, the L-[14C]-arginine uptake by BBMV was reduced by 43.6% at 45 s. 4. It is concluded that L-canavanine inhibits L-arginine Na+-dependent transport across the enterocyte apical membrane in a highly purified intestinal BBMV from broiler chickens.

  14. Novel arginine deiminase-based method to assay L-arginine in beverages.

    PubMed

    Stasyuk, N Ye; Gayda, G Z; Fayura, L R; Boretskyy, Y R; Gonchar, M V; Sibirny, A A

    2016-06-15

    A highly selective and sensitive enzymatic method for the quantitative determination of L-arginine (Arg) has been developed. The method is based on the use of recombinant bacterial arginine deiminase (ADI) isolated from the cells of a recombinant strain Escherichia coli and o-phthalaldehyde (OPA) as a chemical reagent. Ammonia, the product of the enzymatic digestion of Arg by ADI, reacts with OPA and forms in the presence of sulfite a product, which can be detected by spectrophotometry (S) and fluorometry (F). The linear concentration range for Arg assay in the final reaction mixture varies for ADI-OPA-F variant of the method from 0.35 μM to 24 μM with the detection limit of 0.25 μM. For ADI-OPA-S variant of the assay, the linearity varies from 0.7 μM to 50 μM with the detection limit of 0.55 μM. The new method was tested on real samples of wines and juices. A high correlation (R=0.978) was shown for the results obtained with the proposed and the reference enzymatic method.

  15. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L-arginine supplementation.

    PubMed

    Sunderland, Kyle L; Greer, Felicia; Morales, Jacobo

    2011-03-01

    The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean ± SD, age: 36.3 ± 7.9 years; height: 182.4 ± 4.6 cm; and body mass: 79.5 ± 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W·min) before and after 28 days of supplementation with L-arginine (ARG; 2 × 6 g·d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 ± 7.1 ml·kg·min; ARG, 63.5 ± 7.3 ml·kg·min) to postsupplement VO2max (PL, 58.9 ± 6.0 ml·kg·min; ARG, 63.2 ± 7.2 ml·kg·min). Also, no effect was seen from initial VT (PL, 75.7 ± 4.6% VO2max; ARG, 76.0 ± 5.3% VO2max) to postsupplement VT (PL, 74.3 ± 8.1% VO2max; ARG, 74.2 ± 6.4% VO2max). These results indicate that L-arginine does not impact VO2max or VT in trained male cyclists.

  16. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and L-arginine in patients with arteriogenic and non-arteriogenic erectile dysfunction.

    PubMed

    Paroni, R; Barassi, A; Ciociola, F; Dozio, E; Finati, E; Fermo, I; Ghilardi, F; Colpi, G M; Corsi, M M; Melzi d'Eril, G V

    2012-10-01

    The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p < 0.05) and the concentrations in both subgroups were significantly higher than in controls (p < 0.001). There was a negative correlation between ADMA and International Index of Erectile Function Score only in arteriogenic erectile dysfunction subgroup. L-arginine did not differ significantly neither between the two erectile dysfunction subgroups (p > 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p < 0.05) and in non-arteriogenic erectile dysfunction patients (p < 0.05); the two ratios in non-arteriogenic erectile dysfunction patients did not differ from those in the controls (p > 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with

  17. Long-term symptom relief after septoplasty.

    PubMed

    Sundh, Carolina; Sunnergren, Ola

    2015-10-01

    The results for long-term symptom relief after septoplasty are contradictory in reviewed publications but the findings suggest that results are unsatisfactory. In this study, we analyzed and compared short- and long-term symptom relief after septoplasty and factors possibly associated with symptom relief. 111 patients that underwent septoplasty between 2008 and 2010 were included in the study. Medical charts were reviewed for preoperative characteristics and assessments. Data on short-term symptom relief (6 months) were retrieved from the Swedish National Quality Registry for Septoplasty; data on long-term symptom relief (34-70 months) were collected through a questionnaire. Upon the 34-70 month follow-up, 53% of the patients reported that symptoms either remained or had worsened and 83% reported nasal obstruction. Degree of symptom relief was significantly higher among patients not reporting nasal obstruction than among patients reporting nasal obstruction at long-term follow-up. The proportion of patients that reported "my symptoms are gone" declined from 53% after 6 months to 18% after 34-70 months. None of the factors taken into consideration, age at surgery, gender, follow-up time, primary operation/reoperation, history of nasal trauma, self-reported allergy, rhinometric obstruction, or same sided rhinometric, clinical and subjective nasal obstruction were associated with symptom relief. The long-term results after septoplasty are unsatisfactory. A majority of patients report that their symptoms remain after septoplasty.

  18. Long-term outcomes of autoimmune pancreatitis

    PubMed Central

    Ikeura, Tsukasa; Miyoshi, Hideaki; Shimatani, Masaaki; Uchida, Kazushige; Takaoka, Makoto; Okazaki, Kazuichi

    2016-01-01

    Autoimmune pancreatitis (AIP) has been considered a favorable-prognosis disease; however, currently, there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation, exocrine insufficiency, and endocrine insufficiency are observed in 5%-41%, 34%-82%, and 38%-57% of patients having the disease. Furthermore, the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term follow-up. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients, careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed. PMID:27678359

  19. Valuing a long-term care facility.

    PubMed

    Mellen, C M

    1992-10-01

    The business valuation industry generally uses at least one of three basic approaches to value a long-term care facility: the cost approach, sales comparison approach, or income approach. The approach that is chosen and the resulting weight that is applied to it depend largely on the circumstances involved. Because a long-term care facility is a business enterprise, more weight usually is given to the income approach which factors into the estimate of value both the tangible and intangible assets of the facility.

  20. Keratoprosthesis: a long-term review.

    PubMed Central

    Barnham, J. J.; Roper-Hall, M. J.

    1983-01-01

    A keratoprosthesis (KP), is an artificial cornea which is inserted into an opacified cornea in an attempt to restore useful vision or, less commonly, to make the eye comfortable in painful keratopathy. Results o a retrospective study of 35 patients, with 55 KP insertions, are reviewed with regard to visual acuity, length of time vision is maintained, retention time, and complication. Overall there were a number of long-term real successes, eith retention of the KP and maintenance of improved vision in eyes not amenable to conventional treatment. Careful long-term follow-up was needed, with further surgical procedures often being necessary. Images PMID:6860613

  1. Long-term outcomes after severe shock.

    PubMed

    Pratt, Cristina M; Hirshberg, Eliotte L; Jones, Jason P; Kuttler, Kathryn G; Lanspa, Michael J; Wilson, Emily L; Hopkins, Ramona O; Brown, Samuel M

    2015-02-01

    Severe shock is a life-threatening condition with very high short-term mortality. Whether the long-term outcomes among survivors of severe shock are similar to long-term outcomes of other critical illness survivors is unknown. We therefore sought to assess long-term survival and functional outcomes among 90-day survivors of severe shock and determine whether clinical predictors were associated with outcomes. Seventy-six patients who were alive 90 days after severe shock (received ≥1 μg/kg per minute of norepinephrine equivalent) were eligible for the study. We measured 3-year survival and long-term functional outcomes using the Medical Outcomes Study 36-Item Short-Form Health Survey, the EuroQOL 5-D-3L, the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, and an employment instrument. We also assessed the relationship between in-hospital predictors and long-term outcomes. The mean long-term survival was 5.1 years; 82% (62 of 76) of patients survived, of whom 49 were eligible for follow-up. Patients who died were older than patients who survived. Thirty-six patients completed a telephone interview a mean of 5 years after hospital admission. The patients' Physical Functioning scores were below U.S. population norms (P < 0.001), whereas mental health scores were similar to population norms. Nineteen percent of the patients had symptoms of depression, 39% had symptoms of anxiety, and 8% had symptoms of posttraumatic stress disorder. Thirty-six percent were disabled, and 17% were working full-time. Early survivors of severe shock had a high 3-year survival rate. Patients' long-term physical and psychological outcomes were similar to those reported for cohorts of less severely ill intensive care unit survivors. Anxiety and depression were relatively common, but only a few patients had symptoms of posttraumatic stress disorder. This study supports the observation that acute illness severity does not determine long-term outcomes. Even extremely

  2. [Fetal pain: immediate and long term consequences].

    PubMed

    Houfflin Debarge, Véronique; Dutriez, Isabelle; Pusniak, Benoit; Delarue, Eléonore; Storme, Laurent

    2010-06-01

    Several situations are potentially painful for fetuses, such as malformations and invasive procedures. Nociceptive pathways are known to be functional at 26 weeks. Even if it is not possible to evaluate the fetal experience of pain, it is essential to examine its immediate and long-term consequences. As early as the beginning of the second trimester, hemodynamic and hormonal responses are observed following fetal nociceptive stimulation, In experimental studies, long-term changes have been noted in the corticotrop axis, subsequent responses to pain, and behavior after perinatal nociceptive stimulation.

  3. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

    PubMed Central

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

  4. TREATMENT OF MUSCLE MECHANOREFLEX DYSFUNCTION IN HYPERTENSION: EFFECTS OF L-ARGININE DIALYSIS IN THE NUCLEUS TRACTUS SOLITARII

    PubMed Central

    Leal, Anna K.; Mitchell, Jere H.; Smith, Scott A.

    2013-01-01

    The blood pressure response to exercise is exaggerated in hypertension. Recent evidence suggests that an overactive skeletal muscle mechanoreflex contributes significantly to this augmented circulatory responsiveness. Sensory information from the mechanoreflex is processed within the nucleus tractus solitarii (NTS) of the medulla oblongata. Normally, endogenously produced nitric oxide (NO) within the NTS attenuates the increase in mean arterial pressure (MAP) induced by mechanoreflex stimulation. Thus, it has been suggested that decreases in NTS-NO production underlie the generation of mechanoreflex dysfunction in hypertension. Supporting this postulate, it has been shown that blocking NO production within the NTS of normotensive rats reproduces the exaggerated pressor response elicited by mechanoreflex activation in hypertensive animals. What is not known is whether increasing NO production within the NTS of hypertensive rats mitigates mechanoreflex overactivity. In this study, the mechanoreflex was selectively activated by passively stretching hindlimb muscle before and after the dialysis of 1 and 10 μM L-arginine (a NO precursor) within the NTS of decerebrate normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Stretch induced larger elevations in MAP in SHR compared to WKY. In both groups, dialysis of 1 μM L-arginine significantly attenuated the pressor response to stretch. However, at the 10 μM dose, L-arginine had no effect on the MAP response to stretch in WKY while it enhanced the response in SHR. The data demonstrate that increasing NO availability within the NTS using lower doses of L-arginine partially normalizes mechanoreflex dysfunction in hypertension whereas higher doses do not. The findings could prove valuable in the development of treatment options for mechanoreflex overactivity in this disease. PMID:23771911

  5. Increased Plasma Availability of L-arginine in the Postprandial Period Decreases the Postprandial Lipemia in Older Adults

    PubMed Central

    Puga, Guilherme M.; Meyer, Christian; Mandarino, Lawrence J.; Katsanos, Christos S.

    2012-01-01

    Objective Older adults have exaggerated postprandial lipemia (PPL), which increases their risk for cardiovascular disease. We sought to determine the effects of increased plasma L-arginine availability on the oxidation of ingested fat (enriched with [1,1,1-13C]-triolein) and plasma triglyceride (TG) concentrations during the postprandial period in older subjects. Methods On one day, eight healthy subjects (67.8 ± 1.3 years old) received an intravenous infusion of L-arginine during the first hour of the postprandial period (L-ARG), while on a separate day they received saline (control trial; CON). Results The 8-h area under the curve (AUC0–8h) describing the postprandial plasma TG concentrations was considerably lower in the L-ARG trial than the CON trial (−4 ± 21 vs 104 ± 21 mg·dL−1·h; P < 0.01). The rate of the postprandial oxidation of the ingested lipid was not different between the trials, but the average contribution of ingested-oleate to the oleate of TG of the plasma small TG-rich lipoproteins (TRL; Sf = 20–400) was lower in the L-ARG trial (11 ± 1 vs 18 ± 2%; P < 0.01). L-arginine infusion decreased also the AUC0–8h of the plasma free fatty acid concentrations derived from the ingested fat when compared to the saline infusion (0.77±0.09 vs 1.11 ± 0.08; mmol·L−1·h; P < 0.01). Conclusion Increasing the plasma L-arginine availability during the postprandial period decreases the PPL in older adults, in association with a decrease in the postprandial contribution of ingested lipid into TG of the plasma small TRL. PMID:22959634

  6. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    PubMed

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline.

  7. Long-term studies of dopamine agonists.

    PubMed

    Hubble, Jean P

    2002-02-26

    Dopamine agonists have long been used as adjunctive therapy for the treatment of Parkinson's disease (PD). In more recent years these drugs have also been proved safe and effective as initial therapy in lieu of levodopa in the treatment of PD. Long-term levodopa therapy is associated with motor complications, including fluctuating response patterns and dyskinesia. By initially introducing a dopamine agonist as symptomatic drug therapy, it may be possible to postpone the use of levodopa and delay or prevent the development of motor complications. Recently, four clinical trials have explored this hypothesis by comparing the long-term response and side effects of levodopa with dopamine agonist therapy. The drugs studied have included ropinirole, pramipexole, cabergoline, and pergolide. In each of these projects, the occurrence of motor complications, such as wearing off and dyskinesia, was significantly less in the subjects assigned to initiation of therapy with a dopamine agonist. The addition of levodopa could be postponed by many months or even several years. Therefore, these long-term studies of dopamine agonists support the initiation of a dopamine agonist instead of levodopa in an effort to postpone levodopa-related motor complications. This therapeutic approach may be particularly appropriate in PD patients with a long treatment horizon on the basis of age and general good health. The extension phase of the long-term study comparing pramipexole with levodopa is ongoing, and follow-up information may help to establish the value of this treatment strategy.

  8. Long-Term Memory and Learning

    ERIC Educational Resources Information Center

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  9. Who Recommends Long-Term Care Matters

    ERIC Educational Resources Information Center

    Kane, Robert L.; Bershadsky, Boris; Bershadsky, Julie

    2006-01-01

    Purpose: Making good consumer decisions requires having good information. This study compared long-term-care recommendations among various types of health professionals. Design and Methods: We gave randomly varied scenarios to a convenience national sample of 211 professionals from varying disciplines and work locations. For each scenario, we…

  10. Long-term lysimeter data on evapotranspiration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Long term crop evapotranspiration (ET) data measured using large weighing lysimeters have only been gathered in a few places in the world, yet are of great importance for ground truthing of many models of plant water use, mesoscale climate, remote sensing estimation of ET, climate change and climate...

  11. Long-Term Impacts of Educational Interventions

    ERIC Educational Resources Information Center

    Deming, David James

    2010-01-01

    The school accountability movement has led to a marked increase in the use of standardized test scores to measure school and teacher productivity, yet little is known about the correlation between test score gains and improvements in long-term outcomes. In the first chapter of my dissertation, I study the impact of a school choice policy in…

  12. Long-Term Stability of Tutor Performance.

    ERIC Educational Resources Information Center

    Dolmans, Diana H. J. M.; And Others

    1996-01-01

    Examined the extent to which tutor ratings remained stable in the long term by evaluating 291 ratings of 140 tutors at Maastricht University in the Netherlands between 1992 and 1995. The results indicated that, if the aggregated score and overall judgement are used to interpret the precision of individual scores, four and two occasions,…

  13. Long-Term Stability of Social Participation

    ERIC Educational Resources Information Center

    Hyyppa, Markku T.; Maki, Juhani; Alanen, Erkki; Impivaara, Olli; Aromaa, Arpo

    2008-01-01

    The long-term stability of social participation was investigated in a representative urban population of 415 men and 579 women who had taken part in the nationwide Mini-Finland Health Survey in the years 1978-1980 and were re-examined 20 years later. Stability was assessed by means of the following tracking coefficients: kappa, proportion of…

  14. Long-term opioid therapy reconsidered.

    PubMed

    Von Korff, Michael; Kolodny, Andrew; Deyo, Richard A; Chou, Roger

    2011-09-06

    In the past 20 years, primary care physicians have greatly increased prescribing of long-term opioid therapy. However, the rise in opioid prescribing has outpaced the evidence regarding this practice. Increased opioid availability has been accompanied by an epidemic of opioid abuse and overdose. The rate of opioid addiction among patients receiving long-term opioid therapy remains unclear, but research suggests that opioid misuse is not rare. Recent studies report increased risks for serious adverse events, including fractures, cardiovascular events, and bowel obstruction, although further research on medical risks is needed. New data indicate that opioid-related risks may increase with dose. From a societal perspective, higher-dose regimens account for the majority of opioids dispensed, so cautious dosing may reduce both diversion potential and patient risks for adverse effects. Limiting long-term opioid therapy to patients for whom it provides decisive benefits could also reduce risks. Given the warning signs and knowledge gaps, greater caution and selectivity are needed in prescribing long-term opioid therapy. Until stronger evidence becomes available, clinicians should err on the side of caution when considering this treatment.

  15. Professionalism in Long-Term Care Settings

    ERIC Educational Resources Information Center

    Lubinski, Rosemary

    2006-01-01

    Speech-language pathologists who serve elders in a variety of long-term care settings have a variety of professional skills and responsibilities. Fundamental to quality service is knowledge of aging and communication changes and disorders associated with this process, institutional alternatives, and the changing nature of today's elders in…

  16. Long Term Care Aide. Course Outline.

    ERIC Educational Resources Information Center

    Wilbee, Judy

    This course outline is intended to assist the instructor in the development of a curriculum for a long-term care aide program by specifying one component of the curriculum--the objectives. These objectives, or competencies expected as outcomes for student performance on completion of the program, describe the capabilities an individual must…

  17. Evaluating Long-Term Disability Insurance Plans.

    ERIC Educational Resources Information Center

    Powell, Jan

    1992-01-01

    This report analyzes the factors involved in reviewing benefits and services of employer-sponsored group long-term disability plans for higher education institutions. Opening sections describe the evolution of disability insurance and its shape today. Further sections looks at the complex nature of "value" within a plan, relationship…

  18. LONG TERM HYDROLOGICAL IMPACT ASSESSMENT (LTHIA)

    EPA Science Inventory

    LTHIA is a universal Urban Sprawl analysis tool that is available to all at no charge through the Internet. It estimates impacts on runoff, recharge and nonpoint source pollution resulting from past or proposed land use changes. It gives long-term average annual runoff for a lan...

  19. Long-term fixed income market structure

    NASA Astrophysics Data System (ADS)

    Grilli, Luca

    2004-02-01

    Long-term fixed income market securities present a strong positive correlation in daily returns. By using a metrical approach and considering “modified” time series, I show how it is possible to show a more complex structure which depends strictly on the maturity date.

  20. Long-Term Care Research and Policy

    ERIC Educational Resources Information Center

    Kemper, Peter

    2003-01-01

    This article provides a framework for understanding how long-term care (LTC) research contributes to policy, develops a typology of research contributions to policy with examples of each type, and suggests ways to ensure that contributions continue in the future. The article draws on in-depth interviews with LTC experts working at the interface…

  1. The long term characteristics of greenschist

    NASA Astrophysics Data System (ADS)

    Jang, Bo-An

    2016-04-01

    The greenschist in the Jinping II Hydropower Station in southwest China exhibits continuous creep behaviour because of the geological conditions in the region. This phenomenon illustrates the time-dependent deformation and progressive damage that occurs after excavation. In this study, the responses of greenschist to stress over time were determined in a series of laboratory tests on samples collected from the access tunnel walls at the construction site. The results showed that the greenschist presented time-dependent behaviour under long-term loading. The samples generally experienced two stages: transient creep and steady creep, but no accelerating creep. The periods of transient creep and steady creep increased with increasing stress levels. The long-term strength of the greenschist was identified based on the variation of creep strain and creep rate. The ratio of long-term strength to conventional strength was around 80% and did not vary much with confining pressures. A quantitative method for predicting the failure period of greenschist, based on analysis of the stress-strain curve, is presented and implemented. At a confining pressure of 40 MPa, greenschist was predicted to fail in 5000 days under a stress of 290 MPa and to fail in 85 days under the stress of 320 MPa, indicating that the long-term strength identified by the creep rate and creep strain is a reliable estimate.

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

    SciTech Connect

    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

    2010-03-05

    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-{kappa}B) 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-{kappa}B 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-{kappa}B activation and to promote acinar cell proliferation.

  3. Parenteral Administration of l-Arginine Prevents Fetal Growth Restriction in Undernourished Ewes12

    PubMed Central

    Lassala, Arantzatzu; Bazer, Fuller W.; Cudd, Timothy A.; Datta, Sujay; Keisler, Duane H.; Satterfield, M. Carey; Spencer, Thomas E.; Wu, Guoyao

    2010-01-01

    Intrauterine growth restriction (IUGR) is a major health problem worldwide that currently lacks an effective therapeutic solution. This study was conducted with an ovine IUGR model to test the hypothesis that parenteral administration of l-arginine (Arg) is effective in enhancing fetal growth. Beginning on d 28 of gestation, ewes were fed a diet providing 100% (control-fed) or 50% (underfed) of NRC-recommended nutrient requirements. Between d 60 of gestation and parturition, underfed ewes received i.v. infusions of saline or 155 μmol Arg-HCl/kg body weight 3 times daily, whereas control-fed ewes received only saline. The birth weights of lambs from saline-infused underfed ewes were 23% lower (P < 0.01) than those of lambs from control-fed dams. Administration of Arg to underfed ewes increased (P < 0.01) concentrations of Arg (69%), ornithine (55%), proline (29%), methionine (37%), leucine (36%), isoleucine (35%), cysteine (19%), and FFA (43%) in maternal serum, decreased maternal circulating levels of ammonia (18%) and triglycerides (32%), and enhanced birth weights of lambs by 21% compared with saline-infused underfed ewes. There was no difference in birth weights of lambs between the control-fed and the Arg-infused underfed ewes. These novel results indicate that parenteral administration of Arg to underfed ewes prevented fetal growth restriction and provide support for its clinical use to ameliorate IUGR in humans. The findings also lay a new framework for studying cellular and molecular mechanisms responsible for the beneficial effects of Arg in regulating conceptus growth and development. PMID:20505020

  4. Short communication: Nalpha-lauroyl-L-arginine ethylester monohydrochloride reduces bacterial growth in pasteurized milk.

    PubMed

    Woodcock, N H; Hammond, B H; Ralyea, R D; Boor, K J

    2009-09-01

    Effective strategies for extending fluid milk product shelf-life by controlling bacterial growth are of economic interest to the dairy industry. To that end, the effects of addition of l-arginine, Nalpha-lauroyl ethylester monohydrochloride (LAE) on bacterial numbers in fluid milk products were measured. Specifically, LAE was added (125, 170, or 200 mg/L) to conventionally homogenized and pasteurized 3.25% fat chocolate or unflavored milk products. The treated milks and corresponding untreated controls were held at 6 degrees C and plated on standard plate count agar within 24 h of processing and again at 7, 14, 17, and 21 d of storage. Bacterial counts in all unflavored milk samples treated with LAE remained below the Pasteurized Milk Ordinance limit for grade A pasteurized fluid milk of 4.3 log cfu/mL for the entire 21 d. Bacterial counts in unflavored samples containing 170 and 200 mg/L of LAE were significantly lower than those in the untreated unflavored milk at d 17 and 21 postprocessing. Specifically, bacterial counts in the milk treated with 200 mg/L of LAE were 5.77 log cfu/mL lower than in untreated milk at 21 d postprocessing. Bacterial counts in chocolate milk treated with 200 mg/L of LAE were significantly lower than those in the untreated chocolate milk at d 14, 17, and 21. In chocolate milk treated with 200 mg/L of LAE, bacterial counts were 0.9 log cfu/mL lower than in the untreated milk at 21 d postprocessing. Our results show that addition of LAE to milk can reduce bacterial growth. Addition of LAE is more effective at controlling bacterial growth in unflavored milk than in chocolate milk.

  5. Addition of L-arginine to the fertilization medium enhances subsequent bovine embryo development rates.

    PubMed

    Santana, Priscila P B; da Silva, Bruno B; Silva, Thiago V G; Costa, Nathalia N; Cordeiro, Marcela S; Santos, Simone S D; Ohashi, Otávio M; Miranda, Moysés S

    2016-04-01

    Although L-Arginine (ARG) has been reported as a promising bovine sperm capacitation agent, its effects on embryo development are still poorly understood. Herein, we compared the effects of ARG and/or heparin (HEP) addition to the fertilization medium for bovine oocytes on sperm capacitation and embryo development. We chose 10 mM ARG based on blastocyst development rates in a titration experiment. Addition of ARG and/or HEP to the fertilization medium resulted in similar rates of blastocyst development (P > 0.05). However, when ARG, but not HEP, was combined with a nitric oxide (NO) synthase inhibitor (N-Nitro-L-ARG-methyl ester, 10 mM) blastocyst development was decreased (P < 0.05). To assess the effects on capacitation, bovine sperm were incubated for 0, 3, and 6 hours in fertilization medium containing ARG and/or HEP and/or N-Nitro-L-ARG-methyl esterand acrosomal exocytosis rates were evaluated using fluorescein isothiocyanate conjugated Pisum sativum lectin (FITC-PSA) staining and flow cytometry. With HEP, acrosomal exocytosis rates were highest by 3 hours of incubation; however, by 6 hours, rates were similar for HEP and/or ARG (P > 0.05) and higher than those in control media (P < 0.05). Although both ARG and HEP increased sperm NO production (P < 0.05), combination with L-NAME only precluded acrosomal exocytosis when ARG added alone in the medium (P > 0.05). These results suggest that although both ARG and HEP supported sperm capacitation, only the effects of the former were driven via NO production. Moreover, ARG was also as effective as HEP at improving blastocyst development rates. Therefore, ARG may be used as a low-cost alternative sperm capacitation agent for bovine in vitro embryo production.

  6. L-arginine and arginine analogues: effects on isolated blood vessels and cultured endothelial cells.

    PubMed Central

    Schmidt, H. H.; Baeblich, S. E.; Zernikow, B. C.; Klein, M. M.; Böhme, E.

    1990-01-01

    1. The present study examined effects of arginine (Arg) and various Arg analogues on the vascular tone of rabbit and rat aortic rings, the release of nitrite from cultured bovine aortic endothelial cells and the metabolism of L-Arg in bovine and porcine endothelial cell homogenates. The respective D-enantiomers or N-alpha-benzoyl-L-arginine ethyl ester did not substitute for L-Arg. 2. In bovine aortic endothelial cells, the release of nitrite was only observed in the presence of L-Arg or L-Arg methyl ester in the cell culture medium. 3. In dialyzed homogenates of porcine and bovine aortic endothelial cells, L-Arg was metabolized independently of NADPH and Ca2+ to yield L-ornithine (L-Orn) and L-citrulline (L-Cit). No concomitant nitrite formation was detected. 4. Pretreatment of rabbit and rat aortic rings with L-canavanine (L-Can) or NG-monomethyl-L-Arg (L-NMMA) inhibited ATP- and acetylcholine-induced relaxations (endothelium-dependent) but not glyceryltrinitrate-induced relaxations (endothelium-independent). 5. In rabbit aortic rings, Arg and monomeric Arg analogues induced endothelium-independent relaxations. L-Arg methyl ester induced an endothelium-independent contraction, and L-NMMA induced a relaxation in the absence of endothelium and a contraction in the presence of endothelium. Polymeric basic amino acids such as poly L-Arg induced endothelium-dependent relaxations (inhibited by L-Can), a subsequent refractoriness to endothelium-dependent vasodilators (not prevented by L-Can) and endothelial cell death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2282457

  7. Structure of the complex of carboxypeptidase B and N-sulfamoyl-L-arginine.

    PubMed

    Akparov, Valery; Sokolenko, Nikolay; Timofeev, Vladimir; Kuranova, Inna

    2015-10-01

    Porcine pancreatic carboxypeptidase B (EC 3.4.23.6) was complexed with a stable transition-state analogue, N-sulfamoyl-L-arginine, in which an S atom imitates the sp(3)-hybridized carbon in the scissile-bond surrogate. Crystals were grown in a form belonging to the same space group, P41212, as the uncomplexed enzyme. X-ray data were collected to a resolution of 1.25 Å. The molecule was refined and the positions of non-H atoms of the inhibitor and water molecules were defined using difference Fourier maps. The enzyme-inhibitor complex and 329 water molecules were further refined to a crystallographic R factor of 0.159. The differences in conformation between the complexed and uncomplexed forms of carboxypeptidase B are shown. The inhibitor is bound in a curved conformation in the active-site cleft, and the sulfamide group is bound to the Zn ion in an asymmetric bidentate fashion. The complex is stabilized by hydrogen bonds between the N1/N2 guanidine group of the inhibitor and the Asp255 carboxyl of the enzyme. The side-chain CH2 groups of the inhibitor are in van der Waals contact with Leu203 and Ile247 in the enzyme. This study provides useful clues concerning how the transition state of arginine may bind to carboxypeptidase B and therefore provides an insight into the structural basis of carboxypeptidase B selectivity, which is useful for the rational design of a carboxypeptidase with improved selectivity for industrial recombinant pro-insulin processing.

  8. Workshop on long-term contraceptives.

    PubMed

    1996-01-01

    The National Population Council Secretariat (NPCS) of Ghana held a three-day workshop on long-term contraceptives in 1996 in collaboration with the Ministry of Health, the Association of Voluntary Surgical Contraception, and the Johns Hopkins Population Communication Services. The session was funded by USAID. The executive director of NPCS, Dr. Richard Turkson, said that the slow rate of contraceptive acceptance was an obstacle to population control despite political concern that rapid population growth exerted an adverse impact on the economy. Only 10% of married women were using long-term or permanent methods of contraception. The hope was voiced that the participants would devise practical and cost-effective education, information, and communication (IEC) strategies to boost the demand for long-term contraceptive methods among sexually active people in Ghana. It was essential that these strategies and activities were based on a realist assessment of the demographic and social situation of the country. The examination of case studies in cultures similar to Ghana would also offer valuable lessons. The factors that hinder the acceptance of long-term methods include misconceptions, myths, and false rumors rooted in a general lack of knowledge among the people. Participants were urged to come up with strategies to counter these problems, and service providers were encouraged to improve their knowledge about contraceptive methods and counseling skills. Male involvement in contraception was also advocated. Statistics show that most Ghanians practicing contraception were using short-term methods such as foaming tablets, pills, and condoms. However, it is necessary to shift to long-term methods such as injectables, implants, and sterilization in order to achieve significant reductions in fertility.

  9. Long-term biological investigations in space.

    PubMed

    Lotz, R G; Fuchs, H; Bertsche, U

    1975-01-01

    Missions in space within the next two decades will be of longer duration than those carried out up to the present time, and the effects of such long-term flights on biological organisms are unknown. Results of biological experiments that have been performed to date cannot be extrapolated to results in future flights because of the unknown influence of adaptation over a long period of time. Prior experiments with Axolotl, fishes, and vertebrates by our research team (in part with sounding rockets) showed that these specimens did not appear to be suitable for long-term missions on which minimization of expense, technique, and energy is required. Subsequent investigations have shown the suitability of the leech (Hirudo medicinalis), which consumes blood of mammals up to ten times its own weight (1 g) and can live more than 2 years without further food supply. Emphasis in the experiments with Hirudo medicinalis is placed on metabolic rhythm and motility. Resorption and diffusion in tissue, development, and growth under long-term effects of cosmic proton radiation and zero-gravity are other focal points. The constancy of cellular life in the mature animals is a point in favor of these specimens. We have also taken into account the synergistic effects of the space environment on the problems just mentioned. The life-support system constructed for the leech has been tested successfully in four sounding rocket flights and, on that basis, has been prepared for a long-term mission. Long-term investigations out of the terrestrial biosphere will provide us with information concerning the degree of adaptation of certain physiological and biochemical functions and as to what extent biological readjustment or repair processes can occur under the specific stress conditions of space flight.

  10. Case presentation: long-term treatment.

    PubMed

    Glucksman, Myron L

    2013-01-01

    The long-term (14 years) psychodynamic psychotherapy and pharmacotherapy of a depressed, suicidal, self-mutilating female patient is described. Her diagnoses included Chronic Posttraumatic Stress Disorder, Borderline Personality Disorder, and Recurrent Major Depression. Treatment was punctuated with repeated hospitalizations for self-mutilation (cutting) and suicidal ideation. A major determinant for her psychopathology was sexual abuse by her father from ages 6 to 14. This resulted in feelings of guilt and rage that she repressed and acted out through self-mutilating and suicidal behavior. A prolonged negative transference gradually became ambivalent, then positive. This was associated with her internalization of the healing qualities of the therapeutic relationship. She also gained insight into the reasons for her need to punish herself. Her initial self-representation as unworthy and bad was transformed into perceiving herself as a worthwhile, loving person. This case illustrates the role of long-term treatment for a complex, life-threatening, psychiatric disorder.

  11. Long-term sequelae of electrical injury

    PubMed Central

    Wesner, Marni L.; Hickie, John

    2013-01-01

    Abstract Objective To summarize the current evidence-based knowledge about the long-term sequelae of injuries from electrical current. Quality of evidence MEDLINE was searched for English-language articles published in the past 20 years using the following search terms: electrical, injuries, wound, trauma, accident, sequelae, long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to randomly study electrical injury in controlled clinical trials. By necessity, this topic is addressed in less-rigorous observational and retrospective work and case studies. Therefore, the strength of the literature pertaining to the long-term sequelae of electrical injury is impaired by the necessity of retrospective methods and case studies that typically describe small cohorts. Main message There are 2 possible consequences of electrical injury: the person either survives or dies. For those who survive electrical injury, the immediate consequences are usually obvious and often require extensive medical intervention. The long-term sequelae of the electrical injury might be more subtle, pervasive, and less well defined, but can include neurologic, psychological, and physical symptoms. In the field of compensation medicine, determining causation and attributing outcome to an injury that might not result in objective clinical findings becomes a considerable challenge. Conclusion The appearance of these consequences of electrical injury might be substantially delayed, with onset 1 to 5 or more years after the electrical injury. This poses a problem for patients and health care workers, making it hard to ascribe symptoms to a remote injury when they might not arise until well after the incident event. PMID:24029506

  12. Long-term course of opioid addiction.

    PubMed

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  13. Breakthroughs in long term care design.

    PubMed

    Hiatt, L

    1991-01-01

    In summary, here is what design is trying to accomplish in long term care facilities: Functional access; Privacy as entitlement; Sensory optimization to improve vision and hearing; Reduced walking and wheeling distances that still allow people to be mobile; Effective or functional placement of space and equipment; The option of smaller scale, so neither residents nor staff feel like they are hanging out with a unit full of, perhaps 68, people all the time; Flexibility and adaptability

  14. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP) - March 2013.

    PubMed

    Pernod, Gilles; Albaladejo, Pierre; Godier, Anne; Samama, Charles M; Susen, Sophie; Gruel, Yves; Blais, Normand; Fontana, Pierre; Cohen, Ariel; Llau, Juan V; Rosencher, Nadia; Schved, Jean-François; de Maistre, Emmanuel; Samama, Meyer M; Mismetti, Patrick; Sié, Pierre

    2013-01-01

    Direct new oral anticoagulants (NOACs) - inhibitors of thrombin or factor Xa - are intended to be used largely in the treatment of venous thromboembolic disease or the prevention of systematic embolism in atrial fibrillation, instead of vitamin K antagonists. Like any anticoagulant treatment, they are associated with spontaneous or provoked haemorrhagic risk. Furthermore, a significant proportion of treated patients are likely to be exposed to emergency surgery or invasive procedures. Given the absence of a specific antidote, the action to be taken in these situations must be defined. The lack of data means that it is only possible to issue proposals rather than recommendations, which will evolve according to accumulated experience. The proposals presented here apply to dabigatran (Pradaxa(®)) and rivaroxaban (Xarelto(®)); data for apixaban and edoxaban are still scarce. For urgent surgery with haemorrhagic risk, the drug plasma concentration should be less or equal to 30ng/mL for dabigatran and rivaroxaban should enable surgery associated with a high bleeding risk. Beyond that, if possible, the intervention should be postponed by monitoring the drug concentration. The course to follow is then defined according to the NOAC and its concentration. If the anticoagulant dosage is not immediately available, worse propositions, based on the usual tests (prothrombin time and activated partial thromboplastin time), are presented. However, these tests do not really assess drug concentration or the risk of bleeding that depends on it. In case of serious bleeding in a critical organ, the effect of anticoagulant therapy should be reduced using a non-specific procoagulant drug as a first-line approach: activated prothrombin complex concentrate (aPCC) (FEIBA(®) 30-50U/kg) or non-activated PCC (50U/kg). In addition, for any other type of severe haemorrhage, the administration of a procoagulant drug, which is potentially thrombogenic in these patients, is discussed according

  15. Electrodes for long-term esophageal electrocardiography.

    PubMed

    Niederhauser, Thomas; Haeberlin, Andreas; Marisa, Thanks; Jungo, Michael; Goette, Josef; Jacomet, Marcel; Abacherli, Roger; Vogel, Rolf

    2013-09-01

    The emerging application of long-term and high-quality ECG recording requires alternative electrodes to improve the signal quality and recording capability of surface skin electrodes. The esophageal ECG has the potential to overcome these limitations but necessitates novel recorder and lead designs. The electrode material is of particular interest, since the material has to ensure conflicting requirements like excellent biopotential recording properties and inertness. To this end, novel electrode materials like PEDOT and silver-PDMS as well as established electrode materials such as stainless steel, platinum, gold, iridium oxide, titanium nitride, and glassy carbon were investigated by long-term electrochemical impedance spectroscopy and model-based signal analysis using the derived in vitro interfacial properties in conjunction with a dedicated ECG amplifier. The results of this novel approach show that titanium nitride and iridium oxide featuring microstructured surfaces did not degrade when exposed to artificial acidic saliva. These materials provide low electrode potential drifts and insignificant signal distortion superior to surface skin electrodes making them compatible with accepted standards for ambulatory ECG. They are superior to the noble and polarizable metals such as platinum, silver, and gold that induced more signal distortions and are superior to esophageal stainless steel electrodes that corrode in artificial saliva. The study provides rigorous criteria for the selection of electrode materials for prolonged ECG recording by combining long-term in vitro electrode material properties with ECG signal quality assessment.

  16. Long term therapy of generalized anxiety disorder.

    PubMed

    Rouillon, Frédéric

    2004-04-01

    Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

  17. Titanium for long-term tritium storage

    SciTech Connect

    Heung, L.K.

    1994-12-01

    Due to the reduction of nuclear weapon stockpile, there will be an excess of tritium returned from the field. The excess tritium needs to be stored for future use, which might be several years away. A safe and cost effective means for long term storage of tritium is needed. Storing tritium in a solid metal tritide is preferred to storing tritium as a gas, because a metal tritide can store tritium in a compact form and the stored tritium will not be released until heat is applied to increase its temperature to several hundred degrees centigrade. Storing tritium as a tritide is safer and more cost effective than as a gas. Several candidate metal hydride materials have been evaluated for long term tritium storage. They include uranium, La-Ni-Al alloys, zirconium and titanium. The criteria used include material cost, radioactivity, stability to air, storage capacity, storage pressure, loading and unloading conditions, and helium retention. Titanium has the best combination of properties and is recommended for long term tritium storage.

  18. Infective endocarditis: determinants of long term outcome

    PubMed Central

    Netzer, R O M; Altwegg, S C; Zollinger, E; Täuber, M; Carrel, T; Seiler, C

    2002-01-01

    Objective: To evaluate predictors of long term prognosis in infective endocarditis. Design: Retrospective cohort study. Setting: Tertiary care centre. Patients: 212 consecutive patients with infective endocarditis between 1980 and 1995 Main outcome measures: Overall and cardiac mortality; event-free survival; and the following events: recurrence, need for late valve surgery, bleeding and embolic complications, cerebral dysfunction, congestive heart failure. Results: During a mean follow up period of 89 months (range 1–244 months), 56% of patients died. In 180 hospital survivors, overall and cardiac mortality amounted to 45% and 24%, respectively. By multivariate analysis, early surgical treatment, infection by streptococci, age < 55 years, absence of congestive heart failure, and > 6 symptoms or signs of endocarditis during active infection were predictive of improved overall long term survival. Independent determinants of event-free survival were infection by streptococci and age < 55 years. Event-free survival was 17% at the end of follow up both in medically–surgically treated patients and in medically treated patients. Conclusions: Long term survival following infective endocarditis is 50% after 10 years and is predicted by early surgical treatment, age < 55 years, lack of congestive heart failure, and the initial presence of more symptoms of endocarditis. PMID:12067947

  19. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase.

    PubMed Central

    Knowles, R G; Palacios, M; Palmer, R M; Moncada, S

    1989-01-01

    A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological concentrations of free Ca2+ and is inhibited by NG-monomethyl-L-arginine, but not by its enantiomer NG-monomethyl-D-arginine or by L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, or L-arginine methyl ester can replace L-arginine as substrates for the enzyme. These results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to our hypothesis that the formation of NO from L-arginine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase. PMID:2567995

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

    PubMed Central

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

    2017-01-01

    Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring. PMID:28218737

  1. Influence of chemical modification of N alpha-cocoyl-L-arginine ethyl ester on its hepatitis B surface antigen-inactivating effect.

    PubMed Central

    Sugimoto, Y; Toyoshima, S

    1980-01-01

    We have reported previously that N alpha-cocoyl-L-arginine ethyl ester (CAE) strongly inactivates hepatitis B surface antigen (HBsAg; Sugimoto and Toyoshima, Antimicrob. Agents Chemother. 16:329--332, 1979). Replacement of the L-arginine moiety of CAE by L-lysine did not decrease the HBsAg-inactivating effect of CAE, whereas replacement by some neutral amino acids and L-ornithine decreased it. Esterification of the carboxyl group of N alpha-acyl-L-arginine enhanced its inactivating effect. When the ethyl ester of CAE was converted to an amide group, the effect was appreciably decreased. Modification of the carboxyl group was essential for the inactivation. The effectiveness of N alpha-acyl-L-arginine ethyl ester depends upon the length of the acyl group, with the optimum length for the inactivation of HBsAg being C12 to C14. In addition to CAE, N alpha-lauroyl-L-lysine ethyl ester and N alpha-cocoyl-L-arginine amide were found to be strong inactivators of HBsAg. Significant inactivating effects on HBsAg were not observed in many anionic detergents containing an amino acid. These results suggest that for strongly inactivating HBsAg, a compound should contain a special amino acid, such as L-arginine, and a long acyl group and exhibit a cationic property. PMID:7447415

  2. Effect of Exercise Training and L-arginine on Oxidative Stress and Left Ventricular Function in the Post-ischemic Failing Rat Heart.

    PubMed

    Ranjbar, Kamal; Nazem, Farzad; Nazari, Afshin

    2016-04-01

    The aim of the present study was to evaluate the effect of exercise training (ET) and L-arginine on oxidative stress and ventricular function in rat with myocardial infarction (MI). Four weeks after the surgical procedures, 40 Wistar male rats were randomized to the following groups: MI-sedentary (Sed); MI-exercise (Ex); MI-sedentary + L-arginine (Sed + LA); and MI-exercise + L-arginine (Ex + LA); the rats were subjected to aerobic training in the form of treadmill running. Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. Before and after the training program, all subjects underwent resting echocardiography. Catalase (CAT) glutathione peroxidase (GPx), malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Cardiac output, stroke volume and fractional shortening in Ex and Ex + LA groups significantly increased in comparison with the Sed group. Cardiac systolic function indices in Ex + LA group were significantly greater than Ex group. Also, GPx activity and MDA, respectively, increased and decreased in response to ET, but no change was observed in MPO and CAT. These results suggest that ET increased LV function by decreasing oxidative stress and increasing antioxidant defense system in rats with MI. In addition in response to training, L-arginine appears to have additive effect on cardiac function, but have no effect on oxidative stress indices.

  3. Reengineering of a Corynebacterium glutamicum l-Arginine and l-Citrulline Producer▿

    PubMed Central

    Ikeda, Masato; Mitsuhashi, Satoshi; Tanaka, Kenji; Hayashi, Mikiro

    2009-01-01

    Toward the creation of a robust and efficient producer of l-arginine and l-citrulline (arginine/citrulline), we have performed reengineering of a Corynebacterium glutamicum strain by using genetic information of three classical producers. Sequence analysis of their arg operons identified three point mutations (argR123, argG92up, and argG45) in one producer and one point mutation (argB26 or argB31) in each of the other two producers. Reconstitution of the former three mutations or of each argB mutation on a wild-type genome led to no production. Combined introduction of argB26 or argB31 with argR123 into a wild type gave rise to arginine/citrulline production. When argR123 was replaced by an argR-deleted mutation (ΔargR), the production was further increased. The best mutation set, ΔargR and argB26, was used to screen for the highest productivity in the backgrounds of different wild-type strains of C. glutamicum. This yielded a robust producer, RB, but the production was still one-third of that of the best classical producer. Transcriptome analysis revealed that the arg operon of the classical producer was much more highly upregulated than that of strain RB. Introduction of leuC456, a mutation derived from a classical l-lysine producer and provoking global induction of the amino acid biosynthesis genes, including the arg operon, into strain RB led to increased production but incurred retarded fermentation. On the other hand, replacement of the chromosomal argB by heterologous Escherichia coli argB, natively insensitive to arginine, caused a threefold-increased production without retardation, revealing that the limitation in strain RB was the activity of the argB product. To overcome this, in addition to argB26, the argB31 mutation was introduced into strain RB, which caused higher deregulation of the enzyme and resulted in dramatically increased production, like the strain with E. coli argB. This reconstructed strain displayed an enhanced performance, thus

  4. KDP crystal doped with L-arginine amino acid: growth, structure perfection, optical and strength characteristics

    NASA Astrophysics Data System (ADS)

    Pritula, I. M.; Kostenyukova, E. I.; Bezkrovnaya, O. N.; Kolybaeva, M. I.; Sofronov, D. S.; Dolzhenkova, E. F.; Kanaev, A.; Tsurikov, V.

    2016-07-01

    Potassium Dihydrogen Phosphate (KDP) crystal doped with L-arginine (L-arg) amino acid with 1.4 wt% concentration in the solution was grown onto a point seed by the method of temperature reduction. For the first time an attempt was made to grow large-size (7 × 6 × 8 cm3) optically transparent crystals, which allowed to analyze the effect of L-arg additive on the physical properties of the different growth sectors ({100} and {101}) of KDP. The incorporation of L-arg into both growth sectors of the crystal was confirmed by the methods of optical and IR spectroscopy and found to be caused by the ability of the amino acid to form hydrogen bonds with the face {100} and electrostatically interact with the positively charged face {101} of KDP crystal. A slight variation in the unit cell parameters was reported, the elementary cell volume of KDP:L-arg crystal increased in comparison with the one of pure KDP by 2·10-2 and 2.07·10-2 Å3 in the sectors {100} and {101}, respectively. It was found that the doping of L-arg enhanced the SHG efficiency of KDP and depended on the crystal growth sectors. The SHG efficiency of KDP:L-arg was by a factor 2.53 and 3.95 higher in comparison with those of pure KDP for {101} and {100} growth sector, respectively. The doping was found to lead to softening of both faces by ∼3-10% and ∼14-17% in the sectors {101} and {100}, respectively. Investigation of the influence of L-arg molecules on the bulk laser damage threshold of the crystals showed that the bulk laser damage threshold of the samples of KDP:L-arg crystal was higher than the one of the pure crystal in the sector {101} and lower in the sector {100}. The correlation between microhardness and laser damage threshold were discussed. The study is helpful for further searching, designing and simulation of hybrid NLO materials.

  5. Interaction of poly(L-arginine) with negatively charged DPPG membranes: calorimetric and monolayer studies.

    PubMed

    Schwieger, Christian; Blume, Alfred

    2009-08-10

    The interaction of poly(L-arginine) (PLA) with dipalmitoyl-phosphatidylglycerol (DPPG) bilayer membranes and monolayers was studied by differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC), and monolayer experiments. The binding of PLA affected the main transition temperature of lipid bilayers (T(m)) only marginally. Depending on the PLA chain length, T(m) was slightly increased or decreased. This finding was attributed to the superposition of two counteracting effects on the transition after PLA binding. The main transition enthalpy (DeltaH(m)) was decreased upon PLA binding and the formation of a ripple phase (P(beta)') was suppressed. ITC experiments showed that two distinct processes are involved in binding of PLA to gel phase (L(beta)') membranes. At low peptide content the binding reaction is endothermic, and at high peptide concentration the binding becomes exothermic. However, the enthalpy of binding to fluid (L(alpha)) membranes was exothermic for all peptide-to-lipid ratios. The temperature dependence of PLA binding to fluid palmitoyl-oleoyl-phosphatidylglycerol (POPG) membranes showed a decrease in binding enthalpy with increasing temperature (Delta(R)C(p) < 0), indicating hydrophobic contributions to the free energy of binding. For longer PLA chains, the binding enthalpy for L(alpha) membranes was more exothermic than for shorter chains. Monolayer adsorption experiments showed two consecutive binding processes. At low initial surface pressures (pi(0)) a condensation of the lipid film (Deltapi < 0) is first observed after PLA injection into the subphase, followed by an increase in film pressure (Deltapi > 0) due to insertion of peptide side chains into the monolayer. At higher pi(0) only an increase in film pressure can be observed due to the insertion of the side chains. Deltapi increases with increasing pi(0). The insertion of the peptide into the monolayer is corroborated by the observed shift of pi-A isotherms to higher

  6. Dissociation of castor oil-induced diarrhoea and intestinal mucosal injury in rat: effect of NG-nitro-L-arginine methyl ester.

    PubMed Central

    Capasso, F; Mascolo, N; Izzo, A A; Gaginella, T S

    1994-01-01

    1. Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after challenge, which was associated with gross damage to the duodenal and jejunal mucosa. 2. The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury. 3. Intraperitoneal injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg-1 twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg-1) completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4. The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg-1 twice) reversed the effects of L-NAME (50 mg kg-1) on castor oil-induced diarrhoea, gross damage and acid phosphatase release. 5. The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part, the diarrhoea effect of this laxative. PMID:7889264

  7. Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency.

    PubMed

    Al-sharefi, Ahmed; Bilous, Rudy

    2015-09-02

    We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.

  8. Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine.

    PubMed

    Melis, Melania; Arca, Massimiliano; Aragoni, Maria Carla; Cabras, Tiziana; Caltagirone, Claudia; Castagnola, Massimo; Crnjar, Roberto; Messana, Irene; Tepper, Beverly J; Tomassini Barbarossa, Iole

    2015-01-01

    Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva.

  9. Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine

    PubMed Central

    Melis, Melania; Arca, Massimiliano; Aragoni, Maria Carla; Cabras, Tiziana; Caltagirone, Claudia; Castagnola, Massimo; Crnjar, Roberto; Messana, Irene; Tepper, Beverly J.; Tomassini Barbarossa, Iole

    2015-01-01

    Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the –NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a ‘carrier’ of various bitter molecules in saliva. PMID:26103639

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

    SciTech Connect

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

    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

  11. Combined effects of aerobic exercise and l-arginine ingestion on blood pressure in normotensive postmenopausal women: A crossover study.

    PubMed

    Puga, Guilherme M; de P Novais, Iane; Katsanos, Christos S; Zanesco, Angelina

    2016-04-15

    After menopause the incidence of cardiovascular diseases increases in women. A decrease in nitric oxide (NO) bioavailability has been pointed out to play a major role in this phenomenon. Since it is believed that l-arginine administration could improve NO bioavailability, the aim of this study was to examine the effects of acute l-arginine administration associated with aerobic exercise on blood pressure (BP), redox state and inflammatory biomarkers in normotensive postmenopausal women (NPW). Sixteen volunteers (57±6yr) were subjected to four experimental sessions (crossover design): arginine+exercise (A-E); arginine (ARG); exercise+placebo (EXE); control (CON). Each session was initiated with either 9g of l-arginine ingestion (ARG or A-E days), placebo (EXE day), or nothing (CON day). The participants performed 30min of aerobic exercise (A-E and EXE days) or sitting rest (CON and ARG days). Blood samples were collected before each session and 45min after the intervention. Office BP and ambulatory blood pressure monitoring (ABPM) were evaluated. NO/cGMP pathway, redox state and inflammatory biomarkers were measured. Systolic BP decreased during the 24-hour in A-E and EXE sessions. However, diastolic BP reduced only in A-E session. No changes were found in the biomarkers concentrations. In conclusion, the association was effective in lowering diastolic BP in NPW. Additionally, physical exercise alone promoted a long lasting effect on systolic BP measured by ABPM in this population, although this beneficial effect was not associated with changes in the cardio-inflammatory biomarkers. Possibly, other factors such as neural influences could be mediating this effect.

  12. Renal Response to L-Arginine in Diabetic Rats. A Possible Link between Nitric Oxide System and Aquaporin-2

    PubMed Central

    Ortiz, María C.; Albertoni Borghese, María F.; Balonga, Sabrina E.; Lavagna, Agustina; Filipuzzi, Ana L.; Elesgaray, Rosana; Costa, María A.; Majowicz, Mónica P.

    2014-01-01

    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. PMID:25111608

  13. L-Arginine modulates CXC chemokines in the human intestinal epithelial cell line HCT-8 by the NO pathway.

    PubMed

    Marion, Rachel; Coëffier, Moïse; Lemoulan, Sabrina; Gargala, Gilles; Ducrotté, Philippe; Déchelotte, Pierre

    2005-12-01

    Arginine has immunomodulating properties in different animal models but its effects in human intestine remain unknown. This study examined whether arginine modulates inflammatory mediators as chemokines and nitric oxide (NO) in the human intestinal epithelial cell line HCT-8 induced by cytokines. Under basal conditions, arginine did not influence iNOS protein expression, NO and chemokine production and mRNA levels (P>0.05 for all). Stimulation with cytokines-induced a significant increase of NO and chemokine production, iNOS and chemokine mRNA level and iNOS protein expression. Under inflammatory conditions, arginine increased 30% NO production (P<0.05) but did not influence iNOS mRNA level or iNOS protein expression. Under stimulated conditions, arginine decreased IL-8 and Mig mRNA level (57% and 39%, for 0.1 vs. 2 mmol/l l-arginine, P<0.05, respectively), and production (respectively, 28 and 23%, both P<0.05). IP-10 and I-TAC mRNA level and production were not significantly influenced by arginine. Under inflammatory conditions, l-arginine as well as a NO donor (sodium nitroprusside (SNP)) increased NO production, which was inversely correlated with IL-8 production (r'=-0.66, P=0.007 for arginine; r'=-0.79, P<0.0001 for SNP). Use of NG-Methyl-l-arginine acetate, a NOS inhibitor which prevents arginine-induced NO production, suppressed the arginine-induced IL-8 inhibition (P<0.05). In HCT-8 cells, arginine enhanced cytokine-induced NO production, reduced IL-8 and Mig production and mRNA level and had no effects on other assessed chemokines. In conclusion, arginine-induced IL-8 inhibition in HCT-8 cells involves NO pathway under inflammatory conditions. These data suggest that arginine-enriched enteral nutrition may have significant influence on inflammatory response in human intestine.

  14. The protective effect of L-arginine, tadalafil, and their combination in rat testes after ischemia and reperfusion injury

    PubMed Central

    Ozmerdiven, Gokhun; Coskun, Burhan; Kaygisiz, Onur; Vuruskan, Berna Aytac; Asiltas, Burak; Kilicarslan, Hakan

    2017-01-01

    Introduction: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for prevention of the ischemia reperfusion injury after testis torsion in rats. Methods: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue. Spermatogenesis was evaluated with Johnsen’s score. Results: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group in ipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen’s score of the I/R group was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The mean Johnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05). Conclusions: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion. PMID:28163808

  15. Long-Term Wind Power Variability

    SciTech Connect

    Wan, Y. H.

    2012-01-01

    The National Renewable Energy Laboratory started collecting wind power data from large commercial wind power plants (WPPs) in southwest Minnesota with dedicated dataloggers and communication links in the spring of 2000. Over the years, additional WPPs in other areas were added to and removed from the data collection effort. The longest data stream of actual wind plant output is more than 10 years. The resulting data have been used to analyze wind power fluctuations, frequency distribution of changes, the effects of spatial diversity, and wind power ancillary services. This report uses the multi-year wind power data to examine long-term wind power variability.

  16. Transverse dimension and long-term stability.

    PubMed

    Vanarsdall, R L

    1999-09-01

    This article emphasizes the critical importance of the skeletal differential between the width of the maxilla and the width of the mandible. Undiagnosed transverse discrepancy leads to adverse periodontal response, unstable dental camouflage, and less than optimal dentofacial esthetics. Hundreds of adult retreatment patients corrected for significant maxillary transverse deficiency using surgically assisted maxillary expansion (similar to osseous distraction) has produced excellent stability. Eliciting tooth movement for children (orthopedics, lip bumper, Cetlin plate) in all three planes of space by muscles, eruption, and growth, develops the broader arch form (without the mechanical forces of fixed or removable appliances) and has also demonstrated impressive long term stability.

  17. Human Behaviour in Long-Term Missions

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  18. Performance considerations in long-term spaceflight

    NASA Technical Reports Server (NTRS)

    Akins, F. R.

    1979-01-01

    Maintenance of skilled performance during extended space flight is of critical importance to both the health and safety of crew members and to the overall success of mission goals. An examination of long term effects and performance requirements is therefore a factor of immense importance to the planning of future missions. Factors that were investigated include: definition of performance categories to be investigated; methods for assessing and predicting performance levels; in-flight factors which can affect performance; and factors pertinent to the maintenance of skilled performance.

  19. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells.

    PubMed

    Shimomura, Tomoko; Nakano, Tomoyuki; Goto, Kaoru; Wakabayashi, Ichiro

    2017-02-01

    Although diacylglycerol kinase (DGK) is known to be expressed in vascular smooth muscle cell, its functional significance remains to be clarified. We hypothesized that DGK is involved in the pathway of cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells. The purpose of this study was to investigate the effects of R59949, a diacylglycerol kinase inhibitor, on inducible nitric oxide production in vascular smooth muscle cell. Cultured rat aortic smooth muscle cells (RASMCs) were used to elucidate the effects of R59949 on basal and interleukin-1β (IL-1β)-induced NO production. The effects of R59949 on protein and mRNA expression of induced nitric oxide synthase (iNOS) and on transplasmalemmal L-arginine uptake were also evaluated using RASMCs. Treatment of RASMCs with R59949 (10 μM) inhibited IL-1β (10 ng/ml)-induced NO production but not basal NO production. Neither protein nor mRNA expression level of iNOS after stimulation with IL-1β was significantly affected by R59949. Estimated enzymatic activities of iNOS in RASMCs were comparable in the absence and presence of R59949. Stimulation of RASMCs with IL-1β caused a marked increase in transplasmalemmal L-arginine uptake into RASMCs. L-Arginine uptake in the presence of IL-1β was markedly inhibited by R59949, while basal L-arginine uptake was not significantly affected by R59949. Both IL-1β-induced NO production and L-arginine uptake were abolished in the presence of cycloheximide (1 μM). The results indicate that R59949 inhibits inducible NO production through decreasing transplasmalemmal L-arginine uptake. DGK is suggested to be involved in cytokine-stimulated L-arginine transport and regulate its intracellular concentration in vascular smooth muscle cell.

  20. Long term efficacy of a pen injector.

    PubMed

    Dinneen, S F; Cronin, C C; O'Sullivan, D J

    1991-09-01

    We assessed the long term efficacy of Novopen as a form of insulin administration. Records were obtained on 48 patients who were treated with Novopen between January '86 and October '88. Six patients were excluded due to insufficient data. The study group of 42 patients comprised 22 females and 20 males of average age 33 years (range 17-66). Mean Hb.A1 rose from 10.6% to 12.1% after Novopen therapy, a rise of 14.1%. This rise is both clinically and statistically significant (p less than 0.001; 99% confidence limits 0.59-2.78). Increases in weight and insulin dose were also noted, but did not reach statistical significance. The majority of patients felt Novopen was superior to twice daily insulin in terms of ease of administration (81%) and flexibility of lifestyle (95%), and all who were using Novopen wished to continue with it. More than 50% of patients admitted to altering their dietary habits while using Novopen. Despite continuing patient satisfaction with this form of insulin administration, its long-term use may be associated with sub-optimal metabolic control.

  1. Sleep facilitates long-term face adaptation.

    PubMed

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  2. Sleep facilitates long-term face adaptation

    PubMed Central

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition. PMID:23986109

  3. Climate Predictability and Long Term Memory

    NASA Astrophysics Data System (ADS)

    Zhu, X.; Blender, R.; Fraedrich, K.; Liu, Z.

    2010-09-01

    The benefit of climate Long Term Memory (LTM) for long term prediction is assessed using data from a millennium control simulation with the atmosphere ocean general circulation model ECHAM5/MPIOM. The forecast skills are evaluated for surface temperature time series at individual grid points. LTM is characterised by the Hurst exponent in the power-law scaling of the fluctuation function which is determined by detrended fluctuation analysis (DFA). LTM with a Hurst exponent close to 0.9 occurs mainly in high latitude oceans, which are also characterized by high potential predictability. Climate predictability is diagnosed in terms of potentially predictable variance fractions. Explicit prediction experiments for various time steps are conducted on a grid point basis using an auto-correlation (AR1) predictor: in regions with LTM, prediction skills are beyond that expected from red noise persistence; exceptions occur in some areas in the southern oceans and over the northern hemisphere continents. Extending the predictability analysis to the fully forced simulation shows large improvement in prediction skills.

  4. Craniopharyngioma in Children: Long-term Outcomes

    PubMed Central

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  5. Long-Term Care Policy: Singapore's Experience.

    PubMed

    Chin, Chee Wei Winston; Phua, Kai-Hong

    2016-01-01

    Singapore, like many developed countries, is facing the challenge of a rapidly aging population and the increasing need to provide long-term care (LTC) services for elderly in the community. The Singapore government's philosophy on care for the elderly is that the family should be the first line of support, and it has relied on voluntary welfare organizations (VWOs) or charities for the bulk of LTC service provision. For LTC financing, it has emphasized the principles of co-payment and targeting of state support to the low-income population through means-tested government subsidies. It has also instituted ElderShield, a national severe disability insurance scheme. This paper discusses some of the challenges facing LTC policy in Singapore, particularly the presence of perverse financial incentives for hospitalization, the pitfalls of over-reliance on VWOs, and the challenges facing informal family caregivers. It discusses the role of private LTC insurance in LTC financing, bearing in mind demand- and supply-side failures that have plagued the private LTC insurance market. It suggests the need for more standardized needs assessment and portable LTC benefits, with reference to the Japanese Long-Term Care Insurance program, and also discusses the need to provide more support to informal family caregivers.

  6. Long term perfusion system supporting adipogenesis

    PubMed Central

    Abbott, Rosalyn D.; Raja, Waseem K.; Wang, Rebecca Y.; Stinson, Jordan A.; Glettig, Dean L.; Burke, Kelly A.; Kaplan, David L.

    2015-01-01

    Adipose tissue engineered models are needed to enhance our understanding of disease mechanisms and for soft tissue regenerative strategies. Perfusion systems generate more physiologically relevant and sustainable adipose tissue models, however adipocytes have unique properties that make culturing them in a perfusion environment challenging. In this paper we describe the methods involved in the development of two perfusion culture systems (2D and 3D) to test their applicability for long term in vitro adipogenic cultures. It was hypothesized that a silk protein biomaterial scaffold would provide a 3D framework, in combination with perfusion flow, to generate a more physiologically relevant sustainable adipose tissue engineered model than 2D cell culture. Consistent with other studies evaluating 2D and 3D culture systems for adipogenesis we found that both systems successfully model adipogensis, however 3D culture systems were more robust, providing the mechanical structure required to contain the large, fragile adipocytes that were lost in 2D perfused culture systems. 3D perfusion also stimulated greater lipogenesis and lipolysis and resulted in decreased secretion of LDH compared to 2D perfusion. Regardless of culture configuration (2D or 3D) greater glycerol was secreted with the increased nutritional supply provided by perfusion of fresh media. These results are promising for adipose tissue engineering applications including long term cultures for studying disease mechanisms and regenerative approaches, where both acute (days to weeks) and chronic (weeks to months) cultivation are critical for useful insight. PMID:25843606

  7. Long-term experience with indapamide.

    PubMed

    Beling, S; Vukovich, R A; Neiss, E S; Zisblatt, M; Webb, E; Losi, M

    1983-07-01

    Indapamide, 2.5 mg administered once daily for periods up to 36 months, was found to be safe and effective for the long-term control of mild to moderate hypertension. The effects of hydrochlorothiazide, 50 mg, and indapamide, 2.5 mg, were studied in two randomized, double-blind, multicenter trials. Data from the two multicenter trials (20 study sites) were pooled for purposes of comparison. Significant reductions in systolic and diastolic blood pressure, with patients in both supine and standing positions, occurred in both groups within the first 8 weeks of treatment. This effect was maintained throughout the active treatment period. Success, as determined by the therapeutic success rate (percentage of patients with decreases of standing phase V diastolic blood pressure of at least 10 mm Hg or to below 90 mm Hg), occurred in 53% of the patients given hydrochlorothiazide and in 56% of the indapamide-treated patients. During the study period, the nature, frequency, and severity of adverse reactions were similar for both groups. There was no clinically significant difference between the treatment groups for the laboratory assessments. Patients who completed the multicenter trials were eligible for participation in an ongoing long-term extension study of the safety of indapamide. Data are available for periods up to 36 months and demonstrate neither augmentation of clinical or laboratory adverse effects nor any potentially harmful indicators that could be attributed to prolonged treatment.

  8. Clinical review: Long-term noninvasive ventilation

    PubMed Central

    Robert, Dominique; Argaud, Laurent

    2007-01-01

    Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

  9. Long term changes in the polar vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2015-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented.

  10. Long Term Changes in the Polar Vortices

    NASA Astrophysics Data System (ADS)

    Braathen, Geir O.

    2016-04-01

    As the amount of halogens in the stratosphere is slowly declining and the ozone layer slowly recovers it is of interest to see how the meteorological conditions in the vortex develop over the long term since such changes might alter the foreseen ozone recovery. In conjunction with the publication of the WMO Antarctic and Arctic Ozone Bulletins, WMO has acquired the ERA Interim global reanalysis data set for several meteorological parameters. This data set goes from 1979 - present. These long time series of data can be used for several useful studies of the long term development of the polar vortices. Several "environmental indicators" for vortex change have been calculated, and a climatology, as well as trends, for these parameters will be presented. These indicators can act as yardsticks and will be useful for understanding past and future changes in the polar vortices and how these changes affect polar ozone depletion. Examples of indicators are: vortex mean temperature, vortex minimum temperature, vortex mean PV, vortex "importance" (PV*area), vortex break-up time, mean and maximum wind speed. Data for both the north and south polar vortices have been analysed at several isentropic levels from 350 to 850 K. A possible link between changes in PV and sudden stratospheric warmings will be investigated, and the results presented. The unusual meteorological conditions of the 2015 south polar vortex and the 2010/11 and 2015/16 north polar vortices will be compared to other recent years.

  11. Long term effects of Escherichia coli mastitis.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Leitner, Gabriel

    2014-07-01

    Escherichia coli is one of the most frequently diagnosed causes of bovine mastitis, and is typically associated with acute, clinical mastitis. The objective of the present study was to evaluate the long term effects of intramammary infections by E. coli on milk yield and quality, especially milk coagulation. Twenty-four Israeli Holstein cows diagnosed with clinical mastitis due to intramammary infection by E. coli were used in this study. Mean lactation number, days in milk (DIM) and daily milk yield (DMY) at the time of infection was 3.3 ± 1.3, 131.7 days ± 78.6 and 45.7 L ± 8.4, respectively. DMY, milk constituents, somatic cells count (SCC), differential leukocytes count and coagulation parameters were subsequently assessed. Two patterns of inflammation were identified: 'short inflammation', characterized by <15% decrease in DMY and <30 days until return to normal (n = 5), and 'long inflammation', characterized by >15% decrease in DMY and >30 days to reach a new maximum DMY (n = 19). The estimated mean loss of marketable milk during the study was 200 L/cow for 'short inflammation' cases, and 1,500 L/cow for 'long inflammation' ones. Significant differences between 'short' and 'long inflammation' effects were found in almost all parameters studied. Long-term detrimental effects on milk quality were found regardless of clinical or bacteriological cure of affected glands.

  12. Outcomes of long-term audiological rehabilitation in charge syndrome.

    PubMed

    Trevisi, P; Ciorba, A; Aimoni, C; Bovo, R; Martini, A

    2016-06-01

    The aim of this paper is to assess the long-term audiological features and outcomes of hearing rehabilitation in a large group of individuals with CHARGE Syndrome. The study has been conducted retrospectively, on a paediatric patient database, at the Audiology Department of the University Hospitals of Ferrara and Padua. The study sample included 31 children presenting with different degrees of hearing impairment associated with CHARGE syndrome. Hearing was assessed using auditory brainstem responses (ABRs) and/or electrocochleography, or conditioned audiometry (visual reinforcement audiometry [VRA] or play audiometry). Auditory-perceptual outcomes in terms of communication skills and expressive language were also recorded. The effects of hearing rehabilitation (with hearing aids or cochlear implants) in this group of children and language outcomes after rehabilitation were monitored during long-term follow-up. The outcomes of rehabilitation measures differed in relation to the heterogeneous and often severe disabilities associated with CHARGE syndrome, e.g. developmental delay, intellectual delay, visual impairment, thin 8(th) nerve with retrocochlear auditory dysfunction (as described in cases of auditory neuropathy/dyssynchrony). Oral expressive language was severely impaired in most cases, even after lengthy follow-up, suggesting the need for alternative augmentative communication modes. The early identification of sensorineural hearing loss, and carefully planned rehabilitation treatments, can be of some benefit in children with CHARGE syndrome.

  13. Long term differential consequences of miglustat therapy on intestinal disaccharidases.

    PubMed

    Amiri, Mahdi; Naim, Hassan Y

    2014-11-01

    Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50 μM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect.

  14. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 on L-Arginine-Induced Acute Pancreatitis in Rat.

    PubMed

    Mirmalek, Seyed Abbas; Gholamrezaei Boushehrinejad, Ala; Yavari, Hassan; Kardeh, Bahareh; Parsa, Yekta; Salimi-Tabatabaee, Seyed Alireza; Yadollah-Damavandi, Soheila; Parsa, Tina; Shahverdi, Ehsan; Jangholi, Ehsan

    2016-01-01

    This study was aimed at evaluating the protective effect of coenzyme Q10 on L-arginine-induced acute pancreatitis in rats regarding biomarkers and morphologic changes. Thirty-two male Sprague-Dawley rats were divided into 4 equal groups. Control group received intraperitoneal normal saline, while in sham and experimental groups 1 and 2 pancreatitis was induced with L-arginine. E1 and E2 groups were treated with a single dose of 100 and 200 mg/kg Q10, respectively. Serum lipase and amylase, along with pancreas IL-10, IL-1β, and TNF-α, were measured. For evaluation of oxidative stress, pancreatic superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) were assessed. Histopathological examination for morphologic investigation was conducted. Serum amylase and lipase, as well as TNF-α and IL-1β cytokines, reverted with administration of Q10 in consistence with dosage. In contrast, Q10 assisted in boosting of IL-10 with higher dosage (200 mg/kg). A similar pattern for oxidative stress markers was noticed. Both MDA and MPO levels declined with increased dosage, contrary to elevation of SOD and GSH. Histopathology was in favor of protective effects of Q10. Our findings proved the amelioration of pancreatic injury by Q10, which suggest the anti-inflammatory and antioxidant property of Q10 and its potential therapeutic role.

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

    NASA Astrophysics Data System (ADS)

    Liu, Yun; Yang, Yun; Wu, Feng

    2010-04-01

    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.

  16. Nitric oxide control of steroidogenesis: Endocrine effects of N sup G -nitro-L-arginine and comparisons to alcohol

    SciTech Connect

    Adams, M.L.; Nock, B.; Truong, R.; Cicero, T.J. )

    1992-01-01

    Recent studies suggest that nitric oxide (NO) may regulate hormone biosynthesis and secretion. This was tested by treating male rats with N{sup G}-nitro-L-arginine methyl ester (NAME), a NO synthase inhibitor, and measuring serum and testicular interstitial fluid testosterone and serum corticosterone, luteinizing hormone (LH), and prolactin (PRL). The effect of N{sup G}-nitro-L-arginine (NA), a less-soluble form of the same NO synthase inhibitor, on the reproductive suppressant actions of alcohol was also examined. NAME increased testosterone and corticosterone secretion dose-dependently without affecting LH and PRL secretion. The alcohol-induced suppression of testosterone or LH secretion was not altered by treatment with NA. Although effects of NAME and NA on other systems may be involved, these results indicate that testicular and adrenal steroidogenesis are negatively regulated by endogenous NO and that NO does not regulate LH and PRL secretion or inhibit the testicular steroidogenic pathway in the same way as alcohol.

  17. Crystal growth, structural, thermal and mechanical behavior of L-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) single crystals

    NASA Astrophysics Data System (ADS)

    Mahadevan, M.; Ramachandran, K.; Anandan, P.; Arivanandhan, M.; Bhagavannarayana, G.; Hayakawa, Y.

    2014-12-01

    Single crystals of L-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) have been grown successfully from the solution of L-arginine and 4-nitrophenol. Slow evaporation of solvent technique was adopted to grow the bulk single crystals. Single crystal X-ray diffraction analysis confirms the grown crystal has monoclinic crystal system with space group of P21. Powder X-ray diffraction analysis shows the good crystalline nature. The crystalline perfection of the grown single crystals was analyzed by HRXRD by employing a multicrystal X-ray diffractometer. The functional groups were identified from proton NMR spectroscopic analysis. Linear and nonlinear optical properties were determined by UV-Vis spectrophotometer and Kurtz powder technique respectively. It is found that the grown crystal has no absorption in the green wavelength region and the SHG efficiency was found to be 2.66 times that of the standard KDP. The Thermal stability of the crystal was found by obtaining TG/DTA curve. The mechanical behavior of the grown crystal has been studied by Vicker's microhardness method.

  18. Bioinspired synthesis of hydroxyapatite nanocrystals in the presence of collagen and l-arginine: Candidates for bone regeneration.

    PubMed

    Brasinika, Despoina; Tsigkou, Olga; Tsetsekou, Athena; Missirlis, Yiannis F

    2016-04-01

    This work aims at the bioinspired synthesis of hydroxyapatite (HAp) crystals in the presence of both collagen and l-arginine, in an effort to obtain a homogeneous hybrid material, having a bone-like nanostructure. Collagen (Col) is the most commonly utilized protein in most species of life, while L-arginine (Arg) encourages cell attachment, proliferation, and differentiation on HAp surfaces. Transmission electron microscopy, X-ray diffraction and Fourier transform-infrared spectroscopy were used to analyze surface morphology and structure of nanocrystals obtained under different synthesis conditions. It was shown that collagen and arginine content affect HAp crystallization. Collagen has an inhibition effect since HAp crystal size is reduced with the increase of collagen content. The presence of arginine is crucial as a critical content exists (Ca(2+):Arg = 1:1) under which HAp nanocrystals coexist with brushite. Under the optimum synthesis conditions (HAp/Col weight ratio 70/30 and Ca(2+):Arg molar ratio 1:1) HAp nanoplates of a uniform size (around 10 × 10 nm) were obtained. The biocompatibility of this hybrid powder was assessed using human bone marrow derived mesenchymal stem cells (MSCs). Cell response in terms of MSC attachment (scanning electron microscopy) and viability/proliferation (Alamar Blue) demonstrated a noncytotoxic effect of the new material.

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

    PubMed

    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.

  20. Managing soils for long-term productivity

    PubMed Central

    Syers, J. K.

    1997-01-01

    Meeting the goal of long-term agricultural productivity requires that soil degradation be halted and reversed. Soil fertility decline is a key factor in soil degradation and is probably the major cause of declining crop yields. There is evidence that the contribution of declining soil fertility to soil degradation has been underestimated.
    Sensitivity to soil degradation is implicit in the assessment of the sustainability of land management practices, with wide recognition of the fact that soils vary in their ability to resist change and recover subsequent to stress. The concept of resilience in relation to sustainability requires further elaboration and evaluation.
    In the context of soil degradation, a decline in soil fertility is primarily interpreted as the depletion of organic matter and plant nutrients. Despite a higher turnover rate of organic matter in the tropics there is no intrinsic difference between the organic matter content of soils from tropical and temperate regions. The level of organic matter in a soil is closely related to the above and below ground inputs. In the absence of adequate organic material inputs and where cultivation is continuous, soil organic matter declines progressively. Maintaining the quantity and quality of soil organic matter should be a guiding principle in developing management practices.
    Soil microbial biomass serves as an important reservoir of nitrogen (N), phosphorus (P) and sulphur (S), and regulates the cycling of organic matter and nutrients. Because of its high turnover rate, microbial biomass reacts quickly to changes in management and is a sensitive indicator for monitoring and predicting changes in soil organic matter. Modelling techniques have been reasonably successful in predicting changes in soil organic matter with different organic material inputs, but there is little information from the tropics.
    Nutrient depletion through harvested crop components and residue removal, and by leaching and soil

  1. Technology for long-term care.

    PubMed

    Tak, Sunghee H; Benefield, Lazelle E; Mahoney, Diane Feeney

    2010-01-01

    Severe staff shortages in long-term care (LTC) make it difficult to meet the demands of the growing aging population. Further, technology-savvy Baby Boomers are expected to reshape the current institutional environments toward gaining more freedom and control in their care and lives. Voices from business, academia, research, advocacy organizations, and government bodies suggest that innovative technological approaches are the linchpin that may prepare society to cope with these projected demands. In this article, we review the current state of aging-related technology, identify potential areas for efficacy testing on improving the quality of life of LTC residents in future research, and discuss barriers to implementation of LTC technology. Finally, we present a vision of future technology use that could transform current care practices.

  2. Long term performance of radon mitigation systems

    SciTech Connect

    Prill, R.; Fisk, W.J.

    2002-03-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes.

  3. Long-term U. S. energy outlook

    SciTech Connect

    Friesen, G.

    1984-01-01

    Each year Chase Econometrics offers its clients a brief summary of the assumptions underlying the long-term energy forecast for the U.S. To illustrate the uncertainty involved in forecasting for the period to the year 2000, they choose to compare forecasts with some recent projections prepared by the Department of Energy's Office of Policy, Planning and Analysis for the annual National Energy Policy Plan supplement. Particular emphasis is placed on Scenario B, which is the mid-range reference case. As the introduction to the supplement emphasizes, the NEPP projections should not be considered a statement of the policy goals of the Reagan Administration. They represent an analysis of the possible evolution of U.S. energy markets, given current information and existing policies. The purpose of providing Scenario B as a reference case as well as Scenarios A and C as alternate cases is to show the sensitivity of oil price projections to small swings in energy demand.

  4. Withdrawal from long-term benzodiazepine treatment.

    PubMed Central

    Petursson, H; Lader, M H

    1981-01-01

    Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety. PMID:6114776

  5. Long-term control of root growth

    DOEpatents

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  6. [Childhood liver transplantation. Long-term results].

    PubMed

    Jara, Paloma; Hierro, Loreto

    2010-05-01

    Liver transplantation allows long-term survival (10 years or more) in 75% of children receiving transplants before 2000. The risk of mortality after the first year is 4-10% in the next 10-20 years. Chronic rejection affects 6%. The need for late retransplantation is 3-5%. However, the follow-up of these patients involves the management of diverse problems in the graft (immunological, biliary, vascular) and others related to the use of immunosuppressants (renal dysfunction, lymphoproliferative syndrome). The transition from pediatric to adult care generates special needs. Adolescence and young adulthood are associated with a lack of compliance. Adult specialists should be aware of the special features of the original diagnosis and the surgical techniques used in childhood transplantation. Final quality of life is good overall but is lower than that in healthy young persons.

  7. Advanced long term cryogenic storage systems

    NASA Technical Reports Server (NTRS)

    Brown, Norman S.

    1987-01-01

    Long term, cryogenic fluid storage facilities will be required to support future space programs such as the space-based Orbital Transfer Vehicle (OTV), Telescopes, and Laser Systems. An orbital liquid oxygen/liquid hydrogen storage system with an initial capacity of approximately 200,000 lb will be required. The storage facility tank design must have the capability of fluid acquisition in microgravity and limit cryogen boiloff due to environmental heating. Cryogenic boiloff management features, minimizing Earth-to-orbit transportation costs, will include advanced thick multilayer insulation/integrated vapor cooled shield concepts, low conductance support structures, and refrigeration/reliquefaction systems. Contracted study efforts are under way to develop storage system designs, technology plans, test article hardware designs, and develop plans for ground/flight testing.

  8. Reducing long-term reservoir performance uncertainty

    SciTech Connect

    Lippmann, M.J.

    1988-04-01

    Reservoir performance is one of the key issues that have to be addressed before going ahead with the development of a geothermal field. In order to select the type and size of the power plant and design other surface installations, it is necessary to know the characteristics of the production wells and of the produced fluids, and to predict the changes over a 10--30 year period. This is not a straightforward task, as in most cases the calculations have to be made on the basis of data collected before significant fluid volumes have been extracted from the reservoir. The paper describes the methodology used in predicting the long-term performance of hydrothermal systems, as well as DOE/GTD-sponsored research aimed at reducing the uncertainties associated with these predictions. 27 refs., 1 fig.

  9. Long-term monitoring for closed sites

    SciTech Connect

    Golchert, N.W.; Sedlet, J.; Veluri, V.R.

    1985-01-01

    A procedure is presented for planning and implementing a long-term environmental monitoring program for closed low-level radioactive waste disposal sites. The initial task in this procedure is to collect the available information on the legal/regulatory requirements, site and area characteristics, source term, pathway analysis, and prior monitoring results. This information is coupled with parameters such as half-life and retardation factors to develop a monitoring program. As examples, programs are presented for a site that has had little or no waste migration, and for sites where waste has been moved by suface water, by ground water, and by air. Sampling techniques and practices are discussed relative to how a current program would be structured and projections are made on techniques and practices expected to be available in the future. 8 refs., 2 figs.

  10. Neurotoxicity testing during long-term studies.

    PubMed

    Ivens, I

    1990-01-01

    Several tests and methods for the investigation of neurotoxicity were performed with female Wistar rats for up to 187 days. The methods were validated by testing 10 rats treated with beta,beta'-iminodipropionitrile (IDPN) and 10 control rats. Cage side observation of the animals revealed signs of altered behavior and motor dysfunction of the IDPN-treated rats. Results of a neuromuscular screen indicated changes in gait, righting reflex, grip strength and performance of the negative geotropism test. Investigation of the animals in activity monitors and on the accelerating rotarod showed changes of several parameters. The motor nerve conduction velocity, measured 6 months after the first treatment, was reduced by 6.7 meters per second in the IDPN group compared to controls. From the results of the tests it can be concluded that the methods chosen can be used during long-term studies but may be most useful for animals not older than 12 months.

  11. Long term cryogenic storage facility systems study

    NASA Technical Reports Server (NTRS)

    Schuster, John R.

    1987-01-01

    The Long Term Cryogenic Storage Facility Systems Study (LTCSFSS) is a Phase A study of a large capacity propellant depot for the space based, cryogenic orbital transfer vehicle. The study is being performed for Marshall Space Flight Center by General Dynamics Space Systems Division and has five principal objectives: (1) Definition of preliminary concept designs for four storage facility concepts; (2) Selection of preferred concepts through the application of trade studies to candidate propellant management system components; (3) Preparation of a conceptual design for an orbital storage facility; (4) Development of supporting research and technology requirements; and (5) Development of a test program to demonstrate facility performance. The initial study has been completed, and continuation activities are just getting under way to provide greater detail in key areas and accommodate changes in study guidelines and assumptions.

  12. Managing Records for the Long Term - 12363

    SciTech Connect

    Montgomery, John V.; Gueretta, Jeanie

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the Office of Legacy

  13. Posterior urethral valves: long-term outcome.

    PubMed

    Caione, Paolo; Nappo, Simona Gerocarni

    2011-10-01

    Posterior urethral valves represent the most common cause of bladder outlet obstruction in infancy that impairs renal and bladder function. Long-term outcome of patients with previous PUV is evaluated. Patients over 18 years of age, treated from 1982 to 1995 before the age of 3 years were considered. Previous surgery, renal function, bladder activity, urinary incontinence, and fertility/sexual activity were evaluated. Clinical interview, creatinine clearance, uroflowmetry with ultrasound post-void urine residue, and self-administered questionnaire were recorded. Out of 45 identified records, 24 patients (53.3%) accepted to be enrolled (age 18-34 years, mean 23 years). The mean follow-up was 19.5 years (16-30 years). Out of the 21 excluded patients, 20 did not reply to the clinical interview and 1 died at age of 6 years. All the 24 patients had early endoscopic section of PUV; nine also received transient ureterocutaneostomy or vesicostomy. Ureteroneocystostomy was performed in five patients and ureterocystoplasty with unilateral nephrectomy in two. At follow-up chronic renal failure was detected in 13 patients (54.1%) and 9 (37.5%) had arterial hypertension. End-stage renal disease developed in five patients (20.8%): three had successful renal transplantation and two were in dialysis. Lower urinary tract symptoms were present in seven patients (29.1%). No significant fertility deficit and sexual dysfunction were observed in 23 patients, while 1 patient was azoospermic. No paternity was reported so far. Long-term outcome of patients with previously treated PUV is mandatory. Kidney, bladder, and sexual functions should be monitored till adulthood to verify any modified behaviour.

  14. Long-term dynamics of Typha populations

    USGS Publications Warehouse

    Grace, J.B.; Wetzel, R.G.

    1998-01-01

    The zonation of Typha populations in an experimental pond in Michigan was re-examined 15 years after the original sampling to gain insight into the long-term dynamics. Current distributions of Typha populations were also examined in additional experimental ponds at the site that have been maintained for 23 years. The zonation between T. latifolia and T. angustifolia in the previously studied pond 15 years after the initial sampling revealed that the density and distribution of shoots had not changed significantly. Thus, it appears that previously reported results (based on 7- year old populations) have remained consistent over time. Additional insight into the interaction between these two taxa was sought by comparing mixed and monoculture stands in five experimental ponds that have remained undisturbed for their 23-year history. The maximum depth of T. latifolia, the shallow- water species, was not significantly reduced when growing in the presence of the more flood tolerant T. angustifolia. In contrast, the minimum depth of T. angustifolia was reduced from 0 to 37 cm when in the presence of T. latifolia. When total populations were compared between monoculture and mixed stands, the average density of T. angustifolia shoots was 59.4 percent lower in mixed stands while the density of T. latifolia was 32 percent lower, with T. angustifolia most affected at shallow depths (reduced by 92 percent) and T. latifolia most affected at the deepest depths (reduced by 60 percent). These long-term observations indicate that competitive displacement between Typha taxa has remained stable over time.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22512648

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

    PubMed

    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.

  17. Robotics for Long-Term Monitoring

    SciTech Connect

    Shahin, Sarkis; Duran, Celso

    2002-07-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  18. Long-term Changes in Tropospheric Ozone

    NASA Astrophysics Data System (ADS)

    Oltmans, S.; Lefohn, A.; Galbally, I.; Scheel, E.; Bodeker, G.; Brunke, E.; Claude, H.; Tarasick, D.; Simmonds, P.; Anlauf, K.; Schmidlin, F.; Akagi, K.; Redondas, A.

    2006-05-01

    Tropospheric ozone measurements from a selected network of surface and ozonesonde sites are used to give a broad geographic picture of long-term variations. The picture of long-term tropospheric ozone changes is a varied one in terms of both the sign and magnitude of trends and in the possible causes for the changes. At mid latitudes of the S.H. three time series of ~20 years in length agree in showing increases that are strongest in the austral spring (August-October). Profile measurements show this increase extending through the mid troposphere but not into the highest levels of the troposphere. In the N.H. in the Arctic a period of declining ozone in the troposphere through the 1980s into the mid 1990s has reversed and the overall change is small. The decadal-scale variations in the troposphere in this region are related in part to changes in the lowermost stratosphere. At mid latitudes in the N.H., continental Europe and Japan showed significant increases in the 1970s and 1980s. Over North America rises in the 1970s are less than those seen in Europe and Japan, suggesting significant regional differences. In all three of these mid latitude, continental regions tropospheric ozone amounts appear to have leveled off or in some cases declined in the more recent decades. Over the North Atlantic three widely separated sites show significant increases since the late 1990s that may have peaked in recent years. In the N.H. tropics both the surface record and the ozonesondes in Hawaii show a significant increase in the autumn months in the most recent decade compared to earlier periods that drives the overall increase seen in the 30 year record. This appears to be related to a shift in the transport pattern during this season with more frequent flow from higher latitudes in the latest decade. The pattern of change, with the largest increases in the N.H. coming prior to the mid 1980s, suggests that increased positive radiative forcing due to tropospheric ozone was felt

  19. LONG-TERM MONITORING SENSOR NETWORK

    SciTech Connect

    Stephen P. Farrington; John W. Haas; Neal Van Wyck

    2003-10-16

    Long-term monitoring (LTM) associated with subsurface contamination sites is a key element of Long Term Stewardship and Legacy Management across the Department of Energy (DOE) complex. However, both within the DOE and elsewhere, LTM is an expensive endeavor, often exceeding the costs of the remediation phase of a clean-up project. The primary contributors to LTM costs are associated with labor. Sample collection, storage, preparation, analysis, and reporting can add a significant financial burden to project expense when extended over many years. Development of unattended, in situ monitoring networks capable of providing quantitative data satisfactory to regulatory concerns has the potential to significantly reduce LTM costs. But survival and dependable operation in a difficult environment is a common obstacle to widespread use across the DOE complex or elsewhere. Deploying almost any sensor in the subsurface for extended periods of time will expose it to chemical and microbial degradation. Over the time-scales required for in situ LTM, even the most advanced sensor systems may be rendered useless. Frequent replacement or servicing (cleaning) of sensors is expensive and labor intensive, offsetting most, if not all, of the cost savings realized with unattended, in situ sensors. To enable facile, remote monitoring of contaminants and other subsurface parameters over prolonged periods, Applied Research Associates, Inc has been working to develop an advanced LTM sensor network consisting of three key elements: (1) an anti-fouling sensor chamber that can accommodate a variety of chemical and physical measurement devices based on electrochemical, optical and other techniques; (2) two rapid, cost effective, and gentle means of emplacing sensor packages either at precise locations directly in the subsurface or in pre-existing monitoring wells; and (3) a web browser-based data acquisition and control system (WebDACS) utilizing field-networked microprocessor-controlled smart

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

    SciTech Connect

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

    1990-11-01

    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{sup G}-monomethyl-L-arginine. L-Gln also inhibited the conversion of L-({sup 14}C)Cit to L-({sup 14}C)Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor.

  1. Interleukin-2 and concanavalin A upregulate a cat2 isoform encoding a high affinity L-arginine transporter in feline lymphocytes.

    PubMed Central

    Stevens, B R; Tellier, M; Harvey, W; Feldman, D H; Bosworth, J

    2000-01-01

    The immunological responses of activated lymphocytes are associated with increased nitric oxide (NO) biosynthesis. Studies in the literature have primarily approached control of NO by focusing on the regulation of the nitric oxide synthase (NOS) isoforms. However, the present study approaches the control of NO synthesis by addressing the regulation of L-arginine availability to lymphocytes via regulation of membrane transport. The guanidino nitrogen of L-arginine is the sole biosynthetic precursor of NO. We investigated cytokine and mitogen regulation of membrane L-arginine transporters for the first time in feline cells. Feline peripheral blood mononuclear cells were treated with interleukin-2 and concanavalin A, then alternatively spliced isoforms of L-arginine transporters known in other species were probed by RT-PCR, using various oligonucleotide primers that hybridized to several regions in common with the isoforms. Both high affinity and low affinity isoforms are encoded by mRNAs arising from mutually exclusive alternative splicing of the primary transcript. A region of 123 bp was obtained that encoded an extracellular polypeptide loop of 41 amino acids. The sequence of this region represented the high affinity L-arginine substrate binding site of a CAT2 transporter polypeptide isoform, but not the CAT2a isoform low affinity binding site. Neither of the inducible isoforms were constitutively expressed in unstimulated feline cells. This is the first report demonstrating that domestic cats possess the cat2 gene encoding an inducible L-arginine transporter, and, furthermore, that the high affinity isoform transcript is activated by interleukin-2 and concanavalin A in feline lymphocytes. Images Figure 1. Figure 3. PMID:10935886

  2. 22 CFR 228.12 - Long-term leases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Long-term leases. 228.12 Section 228.12 Foreign... Transactions for USAID Financing § 228.12 Long-term leases. Any commodity obtained under a long-term lease..., a long-term lease is defined as a single lease of more than 180 days, or repetitive or...

  3. Evaluating Long-Term Care Through the Humanbecoming Lens.

    PubMed

    Hart, Judith D

    2015-10-01

    The author describes evaluating long-term care from the humanbecoming perspective. Three core ideas are presented related to dignity and living quality, and how the humanbecoming perspective can be incorporated into long-term care evaluations that make a difference to the residents, caregivers, management, and to the outcomes of long-term care. This approach from the humanbecoming perspective can enrich evaluative information, influence long-term care outcomes, and ensure human dignity for all concerned.

  4. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

    PubMed Central

    Perichart-Perera, Otilia; Espino, Salvador; Avila-Vergara, Marco Antonio; Ibarra, Isabel; Ahued, Roberto; Godines, Myrna; Parry, Samuel; Macones, George; Strauss, Jerome F

    2011-01-01

    Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be

  5. Long-term data storage in diamond

    PubMed Central

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies. PMID:27819045

  6. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  7. Long-term potentiation: peeling the onion.

    PubMed

    Nicoll, Roger A; Roche, Katherine W

    2013-11-01

    Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.

  8. Neurological long term consequences of deep diving.

    PubMed Central

    Todnem, K; Nyland, H; Skeidsvoll, H; Svihus, R; Rinck, P; Kambestad, B K; Riise, T; Aarli, J A

    1991-01-01

    Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers. PMID:2025592

  9. Transuranic waste: long-term planning

    SciTech Connect

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig.

  10. Long-Term Consequences of Neonatal Injury

    PubMed Central

    Beggs, Simon

    2015-01-01

    The maturation of the central nervous system’s (CNS’s) sensory connectivity is driven by modality-specific sensory input in early life. For the somatosensory system, this input is the physical, tactile interaction with the environment. Nociceptive circuitry is functioning at the time of birth; however, there is still considerable organization and refinement of this circuitry that occurs postnatally, before full discrimination of tactile and noxious input is possible. This fine-tuning involves separation of tactile and nociceptive afferent input to the spinal cord’s dorsal horn and the maturation of local and descending inhibitory circuitry. Disruption of that input in early postnatal life (for example, by tissue injury or other noxious stimulus), can have a profound influence on subsequent development, and consequently the mature functioning of pain systems. In this review, the impact of neonatal surgical incision on nociceptive circuitry is discussed in terms of the underlying developmental neurobiology. The changes are complex, occurring at multiple anatomical sites within the CNS, and including both neuronal and glial cell populations. The altered sensory input from neonatal injury selectively modulates neuronal excitability within the spinal cord, disrupts inhibitory control, and primes the immune system, all of which contribute to the adverse long-term consequences of early pain exposure. PMID:26174217

  11. [Long-term stability of orthodontic treatment].

    PubMed

    Kuijpers-Jagtman, A M; Al Yami, E A; van 't Hof, M A

    2000-04-01

    Aim of this study was to assess long-term stability of orthodontic treatment in a sample of 1016 patients until 10 years postretention. Treatment outcome was measured with the PAR-index at 6 different stages. The mean age of the patients was 12.0 +/- 3.1 year at the start of treatment to 26.3 +/- 2.9 year 10 years postretention. The results show that 67% of the orthodontic treatment result, as measured with the PAR-index, was maintained 10 years postretention. The PAR-scores for the midline and the open bite remained about the same over the years. However, the scores for the lateral occlusion, overjet, reversed overjet, overbite, and contact point displacement of the upper and lower front teeth increased gradually over time. Nearly 50% of the total relapse took place the first two years after retention. The largest change was found for the position of the lower incisors. Ten years postretention their position was even worse than at the start of treatment.

  12. Long-term in vivo pineal microdialysis.

    PubMed

    Sun, Xing; Liu, Tiecheng; Deng, Jie; Borjigin, Jimo

    2003-09-01

    This study describes the development of a new technique for long-term measurement of daily 5-hydroxytryptamine (5-HT) and melatonin contents in the pineal gland of freely moving rats. The technique features a number of novel improvements over previous protocols. It allows visualization of the pineal gland for accurate targeting of the guide cannula, which minimizes bleeding; incurs no direct injury to the surrounding brain tissues; and causes no interference with the sympathetic innervation from the superior cervical ganglia. Robust releases of melatonin and indole precursors were continuously monitored quantitatively and reproducibly for more than 2 wk in the same animal. In addition, effects of pharmacological agents on in vivo pineal circadian rhythms can be studied reproducibly over time, and gene expression profiles can be correlated with physiological consequences in single animals. Using these approaches, it is found that beta-adrenergic activation leads to decreased release of 5-HT, and that increased cAMP signaling in vivo results in activation of N-acetyltransferase gene induction and melatonin production. These studies will enhance the understanding of signaling pathways that regulate pineal 5-HT and melatonin synthesis and secretion.

  13. Long-term corrosion testing plan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2009-02-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing program. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to accommodate all future testing, given that all testing is consolidated to a single location. This report is a revision to SAND2008-4922 to address DOE comments.

  14. Long-term corrosion testing pan.

    SciTech Connect

    Wall, Frederick Douglas; Brown, Neil R.

    2008-08-01

    This document describes the testing and facility requirements to support the Yucca Mountain Project long-term corrosion testing needs. The purpose of this document is to describe a corrosion testing program that will (a) reduce model uncertainty and variability, (b) reduce the reliance upon overly conservative assumptions, and (c) improve model defensibility. Test matrices were developed for 17 topical areas (tasks): each matrix corresponds to a specific test activity that is a subset of the total work performed in a task. A future document will identify which of these activities are considered to be performance confirmation activities. Detailed matrices are provided for FY08, FY09 and FY10 and rough order estimates are provided for FY11-17. Criteria for the selection of appropriate test facilities were developed through a meeting of Lead Lab and DOE personnel on October 16-17, 2007. These criteria were applied to the testing activities and recommendations were made for the facility types appropriate to carry out each activity. The facility requirements for each activity were assessed and activities were identified that can not be performed with currently available facilities. Based on this assessment, a total of approximately 10,000 square feet of facility space is recommended to meet all future testing needs, given that all testing is consolidated to a single location. This report is a revision to SAND2007-7027 to address DOE comments and add a series of tests to address NWTRB recommendations.

  15. Long-term adequacy of metal resources

    USGS Publications Warehouse

    Singer, D.A.

    1977-01-01

    Although the earth's crust contains vast quantities of metals, extraction technologies and associated costs are inextricably bound to three fundamental geological factors - the amount of metal available in the earth's crust in each range of grades, the mineralogical form and chemical state of the metal, and the spatial distribution of the metal. The energy required to recover a given amount of metal increases substantially as grade declines. Most metal is produced from sulphide or oxide minerals, whereas most metal in the crust may be locked in the structures of the more refractory silicates. Recovery from silicate minerals could require orders of magnitude more energy than that used at present as also could exploitation of small, widely scattered or thin, deeply buried deposits. Although specific information on the fundamental factors is not available, each factor must in turn tend to further restrict exploitation. Independence of average grade and tonnage for many deposit types further reduces the availability of rock as a source of metal. In the long term, effects of these factors will be large increases in price for many metals. ?? 1977.

  16. Long-term data storage in diamond.

    PubMed

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A

    2016-10-01

    The negatively charged nitrogen vacancy (NV(-)) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV(-) optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV(-) ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center's charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV(-) ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  17. Intermediate- and long-term earthquake prediction.

    PubMed Central

    Sykes, L R

    1996-01-01

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study. Images Fig. 1 PMID:11607658

  18. Intermediate- and long-term earthquake prediction.

    PubMed

    Sykes, L R

    1996-04-30

    Progress in long- and intermediate-term earthquake prediction is reviewed emphasizing results from California. Earthquake prediction as a scientific discipline is still in its infancy. Probabilistic estimates that segments of several faults in California will be the sites of large shocks in the next 30 years are now generally accepted and widely used. Several examples are presented of changes in rates of moderate-size earthquakes and seismic moment release on time scales of a few to 30 years that occurred prior to large shocks. A distinction is made between large earthquakes that rupture the entire downdip width of the outer brittle part of the earth's crust and small shocks that do not. Large events occur quasi-periodically in time along a fault segment and happen much more often than predicted from the rates of small shocks along that segment. I am moderately optimistic about improving predictions of large events for time scales of a few to 30 years although little work of that type is currently underway in the United States. Precursory effects, like the changes in stress they reflect, should be examined from a tensorial rather than a scalar perspective. A broad pattern of increased numbers of moderate-size shocks in southern California since 1986 resembles the pattern in the 25 years before the great 1906 earthquake. Since it may be a long-term precursor to a great event on the southern San Andreas fault, that area deserves detailed intensified study.

  19. The long-term variability of Vega

    NASA Astrophysics Data System (ADS)

    Butkovskaya, V.; Plachinda, S.; Valyavin, G.; Baklanova, D.; Lee, B.-C.

    2011-12-01

    Over the time of 60 years Vega (α Lyrae = HD 172167, A0V) has been generally accepted as a standard star in the near-infrared, optical, and ultraviolet regions. But is the spectrophotometric standard Vega really non-variable star? Researchers give very different answers to this question. We aim to search a periodicity in our results of spectropolarimetric study of Vega, namely periodic variations in equivalent width of the spectral lines and longitudinal magnetic field measurements. High-accuracy spectropolarimetric observations of Vega have been performed during 26 nights from 1997 to 2010 using the Coudé spectrograph of the 2.6-m Shain reflector at the Crimean Astrophysical Observatory (CrAO, Ukraine) and during 4 nights in 2007 and 2008 using the echelle spectrograph BOES at the Bohyunsan Optical Astronomy Observatory (BOAO, South Korea). The long-term (year-to-year) variability of Vega was confirmed. It was concluded that this variability does not have magnetic nature. The paper is dedicated to the memory of V.P. Merezhin.

  20. 3 CFR - Long-Term Gulf Coast Restoration Support Plan

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 3 The President 1 2011-01-01 2011-01-01 false Long-Term Gulf Coast Restoration Support Plan Presidential Documents Other Presidential Documents Memorandum of June 30, 2010 Long-Term Gulf Coast... help the Gulf Coast and its people recover from this tragedy. A long-term plan to restore the...

  1. The NMR and X-ray study of L-arginine derived Schiff bases and its cadmium complexes

    NASA Astrophysics Data System (ADS)

    Kołodziej, B.; Grech, E.; Schilf, W.; Kamieński, B.; Pazio, A.; Woźniak, K.

    2014-04-01

    The structure study of five Schiff bases derived from L-arginine (L-Arg) and 2-hydroxy carbonyl compounds were performed in both solution and solid state using NMR and X-ray methods. Both analytical methods applied to the solid state sample of two Schiff bases showed a significant difference in molecular structures of unsubstituted and 7-CH3 substituted compounds. This effect was explained as a steric interaction of methyl group. Additionally the structure of two Cd2+ complexes with some Schiff bases were determined by NMR methods in DMSO solution and in the solid state. On the base of heteronuclear NMR measurement (13C, 15N and 113Cd) it was possible to define the complexation site on nitrogen atom. The large set of spectral parameters: chemical shifts, homo- and heteronuclear coupling constants, were used in structure study.

  2. Toroidal nanostructures from self-assembly of block copolypeptides based on poly(L-arginine) and β-sheet peptide.

    PubMed

    Lim, Yong-beom; Lee, Eunji; Lee, Myongsoo

    2011-01-17

    We demonstrate here that rationally designed block copolypeptides based on poly(L-arginine) and β-sheet peptides can form toroidal nanostructures. In aqueous solution, we found that 1D nanoribbons roll up and connect in an end-to-end fashion under charge-balanced conditions, resulting in the formation of barrel-like toroidal nanostructures. Toroidal diameter was highly uniform (10 nm), indicating that there is a preferred geometrical packing requirement for toroid formation. Our results demonstrate that, when suitably designed, β-sheet nanostructures can be manipulated to form more complex 2D nanostructures. This finding offers new opportunities not only for the fabrication of more sophisticated peptide-based nanobiomaterials, but also for understanding and inhibiting protein misfolding diseases.

  3. The electrostatic driving force for nucleophilic catalysis in L-arginine deiminase: a combined experimental and theoretical study.

    PubMed

    Li, Ling; Li, Zhimin; Wang, Canhui; Xu, Dingguo; Mariano, Patrick S; Guo, Hua; Dunaway-Mariano, Debra

    2008-04-22

    L-arginine deiminase (ADI) catalyzes the hydrolysis of L-arginine to form L-citrulline and ammonia via two partial reactions. A working model of the ADI catalytic mechanism assumes nucleophilic catalysis by a stringently conserved active site Cys and general acid-general base catalysis by a stringently conserved active site His. Accordingly, in the first partial reaction, the Cys attacks the substrate guanidino C zeta atom to form a tetrahedral covalent adduct, which is protonated by the His at the departing ammonia group to facilitate the formation of the Cys- S-alkylthiouronium intermediate. In the second partial reaction, the His activates a water molecule for nucleophilic addition at the thiouronium C zeta atom to form the second tetrahedral intermediate, which eliminates the Cys in formation of the L-citrulline product. The absence of a basic residue near the Cys thiol suggested that the electrostatic environment of the Cys thiol, in the enzyme-substrate complex, stabilizes the Cys thiolate anion. The studies described in this paper explore the mechanism of stabilization of the Cys thiolate. First, the log(k(cat)/K(m)) and log k(cat) pH rate profiles were measured for several structurally divergent ADIs to establish the pH range for ADI catalysis. All ADIs were optimally active at pH 5, which suggested that the Cys pKa is strongly perturbed by the prevailing electrostatics of the ADI active site. The p K a of the Bacillus cereus ADI (BcADI) was determined by UV-pH titration to be 9.6. In contrast, the pKa determined by iodoacetamide Cys alkylation is 6.9. These results suggest that the negative electrostatic field from the two opposing Asp carboxylates perturbs the Cys pKa upward in the apoenzyme and that the binding of the iodoacetamide (a truncated analogue of the citrulline product) between the Cys thiol and the two Asp carboxylates shields the Cys thiol, thereby reducing its pKa. It is hypothesized that the bound positively charged guanidinium group of the

  4. Assessment of serum levels of asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine in coronary artery disease.

    PubMed

    Gad, Mohamed Z; Hassanein, Sally I; Abdel-Maksoud, Sahar M; Shaban, Gamal M; Abou-Aisha, Khaled; Elgabarty, Hossam A

    2010-12-01

    Serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine, and C-reactive protein (hsCRP) levels were assessed in 100 Egyptian male 35-50-year-old patients with coronary artery disease (CAD), classified into: patients under conservative medical treatment, patients directed for percutaneous coronary interventions, patients directed for coronary artery bypass graft operation and patients suffering from acute myocardial infarction. Age- and sex-matched controls (n=100) were included. Correlation between serum levels of biomarkers and dimethylarginine dimethylaminohydrolase-2 (DDAH-2) genotypes was studied. No association between biomarkers and carriage of the specific DDAH2 SNP2 (-449C/G, rs805305) genotype was detected. Further studies are required to confirm the contribution of the biomarkers in the predisposition of CAD.

  5. Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats.

    PubMed

    Utkan, Tijen; Gocmez, Semil S; Regunathan, Soundararajan; Aricioglu, Feyza

    2012-10-01

    Agmatine (l-amino-4-guanidino-butane), a metabolite of L-arginine through the action of arginine decarboxylase, is a novel neurotransmitter. In the present study, effects of agmatine on cognitive functions have been evaluated by using one trial step-down passive avoidance and three panel runway task. Agmatine (20, 40, 80 mg/kg i.p.) was administered either in the presence or absence of a cholinergic antagonist, scopolamine (1 mg/kg i.p.). Scopolamine significantly impaired learning and memory in both passive avoidance and three panel runway test. Agmatine did not affect emotional learning, working and reference memory but significantly improved scopolamine-induced impairment of learning and memory in a dose dependent manner. Our results indicate that agmatine, as an endogenous substance, may have an important role in modulation of learning and memory functions.

  6. An unusual effect of application of the amino acid L-arginine on cat visual cortical cells.

    PubMed

    Rivadulla, C; Grieve, K L; Rodriguez, R; Martinez-Conde, S; Acuña, C; Cuderio, J

    1997-03-03

    Iontophoretic application of L-arginine (L-Arg) resulted in a profound decrease in visually elicited and spontaneous activity in 22 of 77 (29%) cells in area 17 of the anaesthetized/paralysed cat. Duration was long, and cells did not recover pre-application activity levels, indicating permanent decline. This effect was obtained without change in the extracellularly recorded wave-form, demonstrating that this did not result from depolarization block. In the remaining 55 cells, application of L-Arg alone, at levels capable of eliciting inhibition as described above, was without effect. In 29 cells, L-Arg application was able to reverse the effect of inhibition of nitric oxide (NO) production. Populations of cells showing the depressive effect described above and those affected by NO modulation levels were mutually exclusive.

  7. Benzoyl-L-arginine methyl ester (BAME)-esterase activity in human plasma during the gravidic-puerperal cycle.

    PubMed

    Salles Meirelles, R

    1977-01-01

    Benzoyl-L-arginine methyl ester (BAME)-esterase activity of plasma was measured in women going through the gravidic-puerperal cycle and compared with plasma of non-pregnant women. Plasma from women in the 36th to 40th week of pregnancy hydrolyzes BAME two times more rapidly than that from non-pregnant women. During pregnancy, BAME-esterase activity in plasma increases progressively up to the 40th week, decreases during labor, and after delivery reaches the same level as in non-pregnant women. The BAME-esterase activity of plasma was affected by the storage temperature, with differences demonstrable between -20 and -4 C and between pregnant and non-pregnant women.

  8. Crystal growth, structural and thermal studies of amino acids admixtured L-arginine phosphate monohydrate single crystals

    NASA Astrophysics Data System (ADS)

    Anandan, P.; Saravanan, T.; Parthipan, G.; Kumar, R. Mohan; Bhagavannarayana, G.; Ravi, G.; Jayavel, R.

    2011-05-01

    To study the improved characteristics of L-arginine phosphate monohydrate (LAP) crystals, amino acids mixed LAP crystals have been grown by slow cooling method. Amino acids like glycine, L-alanine, and L-valine have been selected for doping. Optical quality bulk crystals have been harvested after a typical growth period of about twenty days. The effect of amino acids in the crystal lattice and molecular vibrational frequencies of various functional groups in the crystals have been studied using X-ray powder diffraction and Fourier Transform infrared (FTIR) analyses respectively. Thermal behavior of the amino acids mixed LAP crystals have been studied from the TG and DTG analyses. High-resolution X-ray diffraction studies have been carried out to find the crystalline nature. Optical transmission studies have been carried out by UV-vis spectrophotometer. The cut off wavelength is below 240 nm for the grown crystals.

  9. In vitro effects of L-arginine on spontaneous and homocysteine-induced contractility of pregnant canine uteri.

    PubMed

    Rizzo, Annalisa; Trisolini, Carmelinda; Spedicato, Massimo; Mutinati, Maddalena; Minoia, Giuseppe; Sciorsci, Raffaele Luigi

    2011-09-01

    The L-Arginine-Nitric Oxide Synthase-Nitric Oxide (L-Arg-NOS-NO) system exerts a pivotal role in the maintenance of uterine quiescence during pregnancy, whereas Homocysteine (Hcy) promotes uterine contractility. The aim of this study was to test the in vitro effects of L-Arg on spontaneous and Hcy-induced contractions of uteri excised from pregnant bitches. 104 strips cut from pregnant uteri were mounted in an organ bath. 40 out of 104 strips (16 from mid-gestation uteri and 24 from close to term uteri, respectively) were exposed to cumulative doses of L-Arg; 40 strips (16 from mid-gestation-uteri and 24 from close to term-uteri, respectively) were exposed to N-nitro-L-arginine methyl ester (L-NAME), a NOS antagonist; the remaining 24 strips (from close-to-term uteri) were first exposed to a single dose of Hcy and then to increasing doses of L-Arg. L-Arg showed no effects on spontaneous contractility both in mid-gestation- and close to term-uterine strips, whereas it promoted a relaxant effect on Hcy-induced contractility. On the contrary, L-NAME increased amplitude of contraction both in mid-gestation and close to term strips. These findings suggest that the L-Arg-NO system is present in the uterus of pregnant bitches and that Hcy is able to modulate its actions. Further investigation of this system may provide the basis of future obstetrical therapies in bitches.

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

    PubMed

    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 < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both 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.

  11. Dietary L-arginine supplementation increases muscle gain and reduces body fat mass in growing-finishing pigs.

    PubMed

    Tan, Bie; Yin, Yulong; Liu, Zhiqiang; Li, Xinguo; Xu, Haijun; Kong, Xiangfeng; Huang, Ruilin; Tang, Wenjie; Shinzato, Izuru; Smith, Stephen B; Wu, Guoyao

    2009-05-01

    Obesity in humans is a major public health crisis worldwide. In addition, livestock species exhibit excessive subcutaneous fat at market weight. However, there are currently few means of reducing adiposity in mammals. This study was conducted with a swine model to test the hypothesis that dietary L-arginine supplementation may increase muscle gain and decrease fat deposition. Twenty-four 110-day-old barrows were assigned randomly into two treatments, representing supplementation with 1.0% L-arginine or 2.05% L-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Growth performance was measured based on weight gain and food intake. After a 60-day period of supplementation, carcass and muscle composition were measured. Serum triglyceride concentration was 20% lower (P < 0.01) but glucagon level was 36% greater (P < 0.05) in arginine-supplemented than in control pigs. Compared with the control, arginine supplementation increased (P < 0.05) body weight gain by 6.5% and carcass skeletal-muscle content by 5.5%, while decreasing (P < 0.01) carcass fat content by 11%. The arginine treatment enhanced (P < 0.05) longissimus dorsi muscle protein, glycogen, and fat contents by 4.8, 42, and 70%, respectively, as well as muscle pH at 45 min post-mortem by 0.32, while reducing muscle lactate content by 37%. These results support our hypothesis that dietary arginine supplementation beneficially promotes muscle gain and reduces body fat accretion in growing-finishing pigs. The findings have a positive impact on development of novel therapeutics to treat human obesity and enhance swine lean-tissue growth.

  12. L-arginine abolishes the hypothalamic serotonergic activation induced by central interleukin-1β administration to normal rats

    PubMed Central

    2013-01-01

    IL-1β-induced anorexia may depend on interactions of the cytokine with neuropeptides and neurotransmitters of the central nervous system control of energy balance and serotonin is likely to be one catabolic mediator targeted by IL-1β. In the complex interplay involved in feeding modulation, nitric oxide has been ascribed a stimulatory action, which could be of significance in counteracting IL-1β effects. The present study aims to explore the participation of the nitric oxide and the serotonin systems on the central mechanisms induced by IL-1β and the relevance of their putative interactions to IL-1β hypophagia in normal rats. Serotonin levels were determined in microdialysates of the ventromedial hypothalamus after a single intracerebroventricular injection of 10 ng of IL-1β , with or without the pre-injection of 20 μg of the nitric oxide precursor L-arginine. IL-1β significantly stimulated hypothalamic serotonin extracellular levels, with a peak variation of 130 ±37% above baseline. IL- 1β also reduced the 4-h and the 24-h food intakes (by 23% and 58%, respectively). The IL-1β-induced serotonergic activation was abolished by the pre-injection of L-arginine while the hypophagic effect was unaffected. The data showed that one central effect of IL-1β is serotonergic stimulation in the ventromedial hypothalamus, an action inhibited by nitric oxide activity. It is suggested that, although serotonin participates in IL-1β anorexia, other mechanisms recruited by IL-1β in normal rats are able to override the absence of the serotonergic hypophagic influence. PMID:24314273

  13. Characterization of local vascular effects of the nitric oxide inhibitor NG-monomethyl-L-arginine on dorsal hand veins.

    PubMed

    Schindler, Christoph; Leuschner, Sven; Schwanebeck, Uta; Kirch, Wilhelm

    2012-06-01

    Infusion of NG-monomethyl-L-arginine (L-NMMA; 6.4 µmol/min) into hand veins can cause a 20% increase in vein size in specific subjects. This study explored potential underlying mechanisms in healthy male participants. Ten healthy male participants received in phenylephrine (PE)-preconstricted veins a dose-response curve (DRC) to L-NMMA (0.2-6.4 µmol/min) without and with coinfusion of the endothelium-dependent dilator histamine, a DRC to L-arginine with and without coinfusion of L-NMMA, a DRC to NG-monomethyl-D-arginine (D-NMMA), and a DRC to L-NMMA in prostaglandin F(2α)-(PGF(2α))-preconstricted veins. Participants were classified as L-NMMA responders (R) and nonresponders (NR). Infusion of L-NMMA resulted in a maximum venodilation of 38% ± 11% (R) versus 10% ± 5% (NR; P = .005). In PGF(2α)-preconstricted veins, L-NMMA caused venodilation to 26% ± 34% (NS) in responders. Results suggest that endothelial nitric oxide synthase-mediated formation of nitric oxide (NO) from L-NMMA in doses >3.2 µmol/min and continuous PE-induced α-adrenergic stimulation resulting in release of very small amounts of NO from L-NMMA contribute to the observed L-NMMA-induced increase in vein size. Venous reactivity to L-NMMA resulting in a phenotype as R or NR is most likely genetically predetermined, which requires further study.

  14. Exercise training in doxorubicin-induced heart failure: effects on the L-arginine-NO pathway and vascular reactivity.

    PubMed

    Matsuura, Cristiane; Brunini, Tatiana M C; Carvalho, Lenize C M M; Resende, Angela C; Carvalho, Jorge J; de Castro, João Pedro Werneck; Mendes-Ribeiro, Antonio C

    2010-01-01

    Heart failure (HF) is the end-stage of cardiovascular disease and is associated with a high incidence of thrombotic events. Nitric oxide (NO) mediates vasodilation and prevents platelet activation, providing an important antithrombotic effect. The aim of this study was to investigate the effects of aerobic training on survival, platelet L-arginine-NO pathway, and vasodilator properties in doxorubicin (DOX)-induced HF. Sprague Dawley rats were randomly assigned to saline/sedentary (SAL/SED), saline/exercise (SAL/EX), DOX/sedentary (DOX/SED), and DOX/exercise (DOX/EX) groups. Four weeks after intraperitoneal DOX injection (1mg/kg(-1)/d(-1); 10 days), shortening fraction in DOX/SED and DOX/EX was significantly reduced. Treadmill exercise was performed during 6 weeks, 5 days/week(-1), 30minutes/day(-1), 50% to 60% of maximum velocity. Survival was higher in DOX/EX (67%) than DOX/SED (33%). No differences were observed in intraplatelet L-arginine transport assessed by incubation with L- [(3)H]-arginine, nor in NOS activity measured by the conversion of L- [(3)H]-arginine into L- [(3)H]-citrulline among the groups. Vasodilation response to acetylcholine was impaired in DOX/SED and DOX/EX; in nitroglycerine, it was limited to DOX/SED. Aerobic training reduced mortality in DOX-induced HF animals and restored vascular smooth muscle relaxation properties. However, it did not ameliorate intraplatelet NO bioavailability and endothelial function during the period studied.

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

    PubMed Central

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

    2014-01-01

    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 < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[3H]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. PMID:24966085

  16. Inhibition of hypoxia-induced relaxation of rabbit isolated coronary arteries by NG-monomethyl-L-arginine but not glibenclamide.

    PubMed Central

    Jiang, C.; Collins, P.

    1994-01-01

    1. The effects of NG-monomethyl-L-arginine, tetrodotoxin and glibenclamide on hypoxia-induced coronary artery relaxation, induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2, were assessed by measuring the changes in isometric tension in isolated epicardial coronary artery rings of the rabbit. In addition, the effects of glibenclamide on the relaxation induced by adenosine were investigated. 2. Hypoxia caused a transient relaxation of 38 +/- 3% (P < 0.01) and 17 +/- 2% (P < 0.01) in endothelium-intact or -denuded arteries respectively. NG-monomethyl-L-arginine (30 and 100 microM) inhibited the relaxation in endothelium-intact rings to 31 +/- 2% (P < 0.05) and 16 +/- 2% (P < 0.01) respectively and slightly but significantly attenuated the relaxation in endothelium-denuded rings to 15 +/- 1% and 13 +/- 1% (P < 0.05) respectively. 3. Glibenclamide, a potassium channel inhibitor, did not significantly after the hypoxia-induced relaxation. 4. Incubation with tetrodotoxin (3 and 10 microM) for 30 min reduced the relaxation to 31 +/- 3% (P < 0.05) and 14 +/- 2% (P < 0.01), and 14 +/- 2% (P < 0.05) and 11 +/- 1% (P < 0.05) in endothelium-intact and -denuded rings respectively. However, indomethacin (10 microM), atropine (1 microM), propranolol (10 microM) and phentolamine (10 microM) did not significantly affect the relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8019749

  17. The role of the NMDA receptors and l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of duloxetine in the forced swimming test.

    PubMed

    Zomkowski, Andréa D E; Engel, Daiane; Cunha, Mauricio P; Gabilan, Nelson H; Rodrigues, Ana Lúcia S

    2012-12-01

    Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as antidepressant. However, its mechanisms of action are not fully understood. This study investigated the effect of duloxetine in the mouse forced swimming test (FST) and in the tail suspension test (TST) and the involvement of the NMDA receptors and the l-arginine-NO-cGMP pathway in its effect in the FST. Duloxetine reduced the immobility time both in the FST and in the TST (dose range of 1-30mg/kg, i.p.), without changing locomotion in an open-field. Duloxetine administered orally (1-30mg/kg) also reduced the immobility time in the FST. The effect of duloxetine (10mg/kg, p.o.) in the FST was prevented by pre-treatment with NMDA (0.1pmol/site, i.c.v.), d-serine (30μg/site, i.c.v.), (l-arginine (750mg/kg, i.p.), S-nitroso-N-acetyl-penicillamine (SNAP, 25μg/site, i.c.v) or sildenafil (5mg/kg, i.p.). The administration of MK-801 (0.001mg/kg, i.p.), 7-nitroindazole (50mg/kg, i.p.), methylene blue (20mg/kg, i.p.) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30pmol/site i.c.v.) in combination with a sub-effective dose of duloxetine (0.3mg/kg, p.o.) reduced the immobility time in the FST. Moreover, the administration of duloxetine (10mg/kg) produced a reduction in NOx levels in the hippocampus and cerebral cortex. Altogether the results suggest that the effect of duloxetine in the FST is dependent on either a blockade of NMDA receptors or an inhibition of NO. In addition, our results further reinforce the role of NMDA receptors and l-arginine-NO-cGMP pathway, besides the monoaminergic systems, in the mechanism of action of current prescribed antidepressant agents.

  18. The neuronal response at extended timescales: long-term correlations without long-term memory

    PubMed Central

    Soudry, Daniel; Meir, Ron

    2014-01-01

    Long term temporal correlations frequently appear at many levels of neural activity. We show that when such correlations appear in isolated neurons, they indicate the existence of slow underlying processes and lead to explicit conditions on the dynamics of these processes. Moreover, although these slow processes can potentially store information for long times, we demonstrate that this does not imply that the neuron possesses a long memory of its input, even if these processes are bidirectionally coupled with neuronal response. We derive these results for a broad class of biophysical neuron models, and then fit a specific model to recent experiments. The model reproduces the experimental results, exhibiting long term (days-long) correlations due to the interaction between slow variables and internal fluctuations. However, its memory of the input decays on a timescale of minutes. We suggest experiments to test these predictions directly. PMID:24744724

  19. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    NASA Astrophysics Data System (ADS)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  20. Long-term suppression of infection in total joint arthroplasty.

    PubMed

    Rao, Nalini; Crossett, Lawrence S; Sinha, Raj K; Le Frock, Jack L

    2003-09-01

    Optimal treatment for a chronic infected prosthesis is the removal of infected and necrotic tissue and all the components of the prosthesis with staged revision in conjunction with systemic antibiotics. If this is not possible because of the poor general condition of the patient, because of unacceptable functional results secondary to removal of the prosthesis, or because the patient refuses surgery in an attempt to salvage the infected prosthesis, a reasonable alternative is long-term oral suppressive antibiotic therapy for maintenance of a functioning prosthesis. Prompt recognition with rapid debridement and initiation of antibiotic therapy seems crucial. Our study confirms a favorable outcome of maintenance of functioning prostheses in 86.2% of patients after a mean followup of 5 years. All patients had initial debridement with 4 to 6 weeks of systemic antibiotic therapy. Advanced age did not seem to predict poor outcome. Joint location, duration of symptoms, and the time of onset of infection did not predict success or failure. The overall success rate for Staphylococcus aureus prosthetic joint infection was 69% after a mean followup of 5 years. The ideal regimen and optimal duration of oral suppressive therapy for a favorable outcome is not well-established and needs additional data with prospective multicenter studies.

  1. Modeling maintenance of long-term potentiation in clustered synapses: long-term memory without bistability.

    PubMed

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the "clustered plasticity hypothesis" which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.

  2. Modeling Maintenance of Long-Term Potentiation in Clustered Synapses: Long-Term Memory without Bistability

    PubMed Central

    Smolen, Paul

    2015-01-01

    Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (>1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the “clustered plasticity hypothesis” which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory. PMID:25945261

  3. LONG TERM IN SITU DISPOSAL ENGINEERING STUDY

    SciTech Connect

    ADAMS; CARLSON; BROCKMAN

    2003-07-23

    Patent application pulled per Ken Norris (FH General Counsel). The objective of this study is to devise methods, produce conceptual designs, examine and select alternatives, and estimate costs for the demonstration of long-term (300-year) in situ disposal of an existing waste disposal site. The demonstration site selected is the 216-A-24 Crib near the 200 East Area. The site contains a fission product inventory and has experienced plant, animal, and inadvertent than intrusion. Of the potential intrusive events and transport pathways at the site, potential human intrusion has been given primary consideration in barrier design. Intrusion by wind, plants, and animals has been given secondary consideration. Groundwater modeling for a number of barrier configurations has been carried out to help select a barrier that will minimize water infiltration and waste/water contact time. The estimated effective lifetime and cost of 20 barrier schemes, using a variety of materials, have been evaluated. The schemes studied include single component surface barriers, multicomponent barriers, and massively injected grout barriers. Five barriers with high estimated effective lifetimes and relatively low costs have been selected for detailed evaluation. They are basalt riprap barriers, massive soil barriers, salt basin barriers, multi-component fine/coarse barriers, and cemented basalt barriers. A variety of materials and configurations for marking the site have also been considered. A decision analysis was completed to select a barrier scheme for demonstration. The analysis indicated that the basalt riprap alternative would be the preferred choice for a full-scale demonstration. The recommended approach is to demonstrate the basalt riprap barrier at the 216-A-24 Crib as soon as possible. Methods and costs of assessing effectiveness of the demonstration are also described. Preliminary design modifications and costs for applying the five selected barrier schemes to other site types are

  4. Long term cultivation of larger benthic Foraminifera

    NASA Astrophysics Data System (ADS)

    Wöger, Julia; Eder, Wolfgang; Kinoshita, Shunichi; Antonino, Briguglio; Carles, Ferrandes-Cañadell; Hohenegger, Johann

    2015-04-01

    Benthic Foraminifera are used in a variety of applications employing numerous different methods, i.e. ecological monitoring, studying the effects of ocean acidification, reconstructing palaeo-bathymetry or investigating palaeo-salinity and palaeo-temperature to name only a few. To refine our understanding of ecological influences on larger benthic foraminiferal biology and to review inferences from field observations, culture experiments have become an indispensable tool. While culture experiments on smaller benthic foraminifera have become increasingly frequent in the past century, reports of the cultivation of symbiont bearing larger Foraminifera are rare. Generally, cultivation experiments can be divided into two groups: Culturing of populations and cultivation of single specimens allowing individual investigation. The latter differ form the former by several restrictions resulting from the need to limit individual motility without abridging microenvironmental conditions in the Foraminiferans artificial habitat, necessary to enable the individual to development as unfettered as possible. In this study we present first experiences and preliminary results of the long-term cultivation of larger benthic Foraminifera conducted at the 'Tropical Biosphere Research Station Sesoko Island, University of the Ryukyus', Japan, trying to reproduce natural conditions as closely as possible. Individuals of three species of larger benthic Foraminifera (Heterostegina depressa, Palaeonummulites venosus and Operculina complanata) have been cultured since April 2014. At the time of the general assembly the cultivation experiments will have been going on for more than one year, with the aim to investigate growth rates, longevities and reproduction strategies for comparison with results statistically inferred from application of the of the 'natural laboratory' method. The most important factor influencing foraminiferal health and development was found to be light intensity and light

  5. A security/safety survey of long term care facilities.

    PubMed

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

  6. Pulmonary complications after long term amiodarone treatment.

    PubMed Central

    Roca, J; Heras, M; Rodriguez-Roisin, R; Magriñà, J; Xaubet, A; Sanz, G

    1992-01-01

    BACKGROUND: Amiodarone hydrochloride is an antiarrhythmic agent useful in arrhythmias refractory to standard therapy. Although interstitial pneumonitis is known to be its most serious side effect, several aspects of amiodarone lung toxicity are still controversial. METHODS: Pulmonary side effects were examined in a sample of 61 symptomless patients (mean (SD) age 55 (7) years) who had had long term treatment with amiodarone (daily maintenance dose 400 mg), selected from 482 men attending the University of Barcelona myocardial infarction project. To allow for the confounding effects of coronary artery disease and tobacco history on lung function, 46 patients who had taken amiodarone for more than one year were matched with a control group from the same population. Subjects underwent measurement of lung volumes, arterial blood gas analysis and an incremental bicycle exercise test. RESULTS: Most lung function values were close to predicted values, though there was a small increase in resting alveolar-arterial oxygen tension difference (A-aDO2) at rest (4.8 (1.4) kPa in both groups). There were no differences in the results of forced spirometry or static lung volumes between the two groups, or in the fall in A-aDO2 from rest to exercise. There was a small difference between the amiodarone and the control group in transfer factor for carbon monoxide corrected for lung volume (KCO 1.67 (0.3) and 1.83 (0.3) mmol min-1 kPa-1 l-1 respectively) and in exercise capacity (140 (25) and 120 (30)w). Only three patients showed lung function impairment consistent with pneumonitis. No relation between lung function measures and cumulative doses of amiodarone or desethylamiodarone was found. CONCLUSIONS: The prevalence of clinically evident pulmonary side effects was 4.9%, which is lower than that reported in studies in which higher daily maintenance doses of amiodarone were given. The slightly lower KCO values and lower work load achieved by the patients taking amiodarone suggest a

  7. LOP- LONG-TERM ORBIT PREDICTOR

    NASA Technical Reports Server (NTRS)

    Kwok, J. H.

    1994-01-01

    The Long-Term Orbit Predictor (LOP) trajectory propagation program is a useful tool in lifetime analysis of orbiting spacecraft. LOP is suitable for studying planetary orbit missions with reconnaissance (flyby) and exploratory (mapping) trajectories. Sample data is included for a geosynchronous station drift cycle study, a Venus radar mapping strategy, a frozen orbit about Mars, and a repeat ground trace orbit. LOP uses the variation-of-parameters method in formulating the equations of motion. Terms involving the mean anomaly are removed from numerical integrations so that large step sizes, on the order of days, are possible. Consequently, LOP executes much faster than programs based on Cowell's method, such as the companion program ASAP (the Artificial Satellite Analysis Program, NPO-17522, also available through COSMIC). The program uses a force model with a gravity field of up to 21 by 21, lunisolar perturbation, drag, and solar radiation pressure. The input includes classical orbital elements (either mean or oscillating), orbital elements of the sun relative to the planet, reference time and dates, drag coefficients, gravitational constants, planet radius, rotation rate. The printed output contains the classical elements for each time step or event step, and additional orbital data such as true anomaly, eccentric anomaly, latitude, longitude, periapsis altitude, and the rate of change per day of certain elements. Selected output is additionally written to a plot file for postprocessing by the user. LOP is written in FORTRAN 77 for batch execution on IBM PC compatibles running MS-DOS with a minimum of 256K RAM. Recompiling the source requires the Lahey F77 v2.2 compiler. The LOP package includes examples that use LOTUS 1-2-3 for graphical displays, but any graphics software package should be able to handle the ASCII plot file. The program is available on two 5.25 inch 360K MS-DOS format diskettes. The program was written in 1986 and last updated in 1989. LOP is

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

    PubMed Central

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

    2016-01-01

    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. PMID:27582465

  9. Reengineering of the feedback-inhibition enzyme N-acetyl-L-glutamate kinase to enhance L-arginine production in Corynebacterium crenatum.

    PubMed

    Zhang, Jingjing; Xu, Meijuan; Ge, Xiaoxun; Zhang, Xian; Yang, Taowei; Xu, Zhenghong; Rao, Zhiming

    2017-02-01

    N-acetyl-L-glutamate kinase (NAGK) catalyzes the second step of L-arginine biosynthesis and is inhibited by L-arginine in Corynebacterium crenatum. To ascertain the basis for the arginine sensitivity of CcNAGK, residue E19 which located at the entrance of the Arginine-ring was subjected to site-saturated mutagenesis and we successfully illustrated the inhibition-resistant mechanism. Typically, the E19Y mutant displayed the greatest deregulation of L-arginine feedback inhibition. An equally important strategy is to improve the catalytic activity and thermostability of CcNAGK. For further strain improvement, we used site-directed mutagenesis to identify mutations that improve CcNAGK. Results identified variants I74V, F91H and K234T display higher specific activity and thermostability. The L-arginine yield and productivity of the recombinant strain C. crenatum SYPA-EH3 (which possesses a combination of all four mutant sites, E19Y/I74V/F91H/K234T) reached 61.2 and 0.638 g/L/h, respectively, after 96 h in 5 L bioreactor fermentation, an increase of approximately 41.8% compared with the initial strain.

  10. Beneficial effects of L-arginine on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuronal degeneration in substantia nigra of Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Nezhad, Saeed Vafaei; Shahi, Sekineh; Lotfi, Nassim; Ehsani, Hossein; Sadeghi, Akram

    2016-01-01

    Background: L-arginine has been recently investigated and proposed to reduce neurological damage after various experimental models of neuronal cellular damage. In this study, we aim to evaluate the beneficial effects of L-arginine administration on the numerical density of dark neurons (DNs) in the substantia nigra pars compacta (SNc) of Balb/c mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Materials and Methods: Male Balb/c mice were randomly divided into 4 groups (n = 7 each): MPTP only; saline only (control); MPTP + L-arginine; and L-arginine only. The animals were infused intranasally with a single intranasal administration of the proneurotoxin MPTP (1 mg/nostril). L-arginine (300 mg/kg) was administrated intraperitoneally once daily for 1-week starting from 3 days after MPTP administration. Cavalieri principle method was used to estimate the numerical density of DNs in the SNc of different studied groups. Results: Twenty days following MPTP administration, the number of DNs was significantly increased when compared to sham-control and L-arginine-control groups (P < 0.05). Nevertheless, our results showed that L-arginine administration significantly decreased the numerical density of DNs in SNc of mice. Conclusion: This investigation provides new insights in experimental models of Parkinson’s disease, indicating that L-arginine represents a potential treatment agent for dopaminergic neuron degeneration in SNc observed in Parkinson’s disease patients. PMID:27656609

  11. NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

    PubMed

    Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2016-01-15

    We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each other's responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms.

  12. Nitric Oxide Is Associated with Long-Term Zinc Tolerance in Solanum nigrum1[W

    PubMed Central

    Xu, Jin; Yin, Hengxia; Li, Yulong; Liu, Xiaojing

    2010-01-01

    Nitric oxide (NO) has been identified as a signal molecule that interplays with reactive oxygen species in response to heavy metal stresses. Roles of NO in regulating cadmium toxicity and iron deficiency have been proposed; however, the function of NO in zinc (Zn) tolerance in plants remains unclear. Here, we investigated NO accumulation and its role in plant Zn tolerance. Zn-induced NO production promoted an increase in reactive oxygen species accumulation in Solanum nigrum roots by modulating the expression and activity of antioxidative enzymes. Subsequently, programmed cell death (PCD) was observed in primary root tips. Inhibiting NO accumulation by 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (a specific NO scavenger) or NG-nitro-l-arginine-methyl ester (a NO synthase inhibitor) prevented the increase of superoxide radical and hydrogen peroxide as well as the subsequent cell death in the root tips, supporting the role of NO in Zn-induced PCD in the root tips. Zn-induced NO production affected the length of primary roots, the number of lateral roots, and root hair growth and thereby modulated root system architecture and activity. Investigation of metal contents in Zn-treated roots suggests that NO is required for metal (especially iron) uptake and homeostasis in plants exposed to excess Zn. Taken together, our results indicate that NO production and the subsequent PCD in root tips exposed to excess Zn are favorable for the S. nigrum seedling response to long-term Zn toxicity by modulating root system architecture and subsequent adaptation to Zn stress. PMID:20855519

  13. L-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway.

    PubMed

    Ma, Xi; Han, Meng; Li, Defa; Hu, Shengdi; Gilbreath, Kyler R; Bazer, Fuller W; Wu, Guoyao

    2017-03-04

    L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. L-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 μmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 μmol L-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70(S6K) and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.

  14. Role of adenosine transport in gestational diabetes-induced l-arginine transport and nitric oxide synthesis in human umbilical vein endothelium

    PubMed Central

    Vásquez, Gustavo; Sanhueza, Felipe; Vásquez, Rodrigo; González, Marcelo; Martín, Rody San; Casanello, Paola; Sobrevia, Luis

    2004-01-01

    Gestational diabetes is associated with increased l-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial l-arginine/NO pathway via A2 purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 μm), and intracellular l-arginine (1.9 mm) and l-citrulline (0.7 mm) levels compared with normal cells (0.05 μm, 0.89 mm, 0.35 mm, respectively). Incubation of HUVEC from normal pregnancies with 1 μm nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44mapk activation, and were blocked by the A2a purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the l-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A2a purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation of l-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus. PMID:15272035

  15. Stochastic Induction of Long-Term Potentiation and Long-Term Depression

    PubMed Central

    Antunes, G.; Roque, A. C.; Simoes-de-Souza, F. M.

    2016-01-01

    Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje cell synapses are persistent synaptic alterations induced by high and low rises of the intracellular calcium ion concentration ([Ca2+]), respectively. The occurrence of LTD involves the activation of a positive feedback loop formed by protein kinase C, phospholipase A2, and the extracellular signal-regulated protein kinase pathway, and its expression comprises the reduction of the population of synaptic AMPA receptors. Recently, a stochastic computational model of these signalling processes demonstrated that, in single synapses, LTD is probabilistic and bistable. Here, we expanded this model to simulate LTP, which requires protein phosphatases and the increase in the population of synaptic AMPA receptors. Our results indicated that, in single synapses, while LTD is bistable, LTP is gradual. Ca2+ induced both processes stochastically. The magnitudes of the Ca2+ signals and the states of the signalling network regulated the likelihood of LTP and LTD and defined dynamic macroscopic Ca2+ thresholds for the synaptic modifications in populations of synapses according to an inverse Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion, our model presents a unifying mechanism that explains the macroscopic properties of LTP and LTD from their dynamics in single synapses. PMID:27485552

  16. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation.

    PubMed

    Artola, A; Singer, W

    1993-11-01

    In many brain areas, including the cerebellar cortex, neocortex, hippocampus, striatum and nucleus accumbens, brief activation of an excitatory pathway can produce long-term depression (LTD) of synaptic transmission. In most preparations, induction of LTD has been shown to require a minimum level of postsynaptic depolarization and a rise in the intracellular Ca2+ concentration [Ca2+]i in the postsynaptic neurone. Thus, induction conditions resemble those described for the initiation of associative long-term potentiation (LTP). However, data from structures susceptible to both LTD and LTP suggest that a stronger depolarization and a greater increase in [Ca2+]i are required to induce LTP than to initiate LTD. The source of Ca2+ appears to be less critical for the differential induction of LTP and LTD than the amplitude of the Ca2+ surge, since the activation of voltage- and ligand-gated Ca2+ conductances as well as the release from intracellular stores have all been shown to contribute to both LTD and LTP induction. LTD is induceable even at inactive synapses if [Ca2+]i is raised to the appropriate level by antidromic or heterosynaptic activation, or by raising the extracellular Ca2+ concentration [Ca2+]o. These conditions suggest a rule (called here the ABS rule) for activity-dependent synaptic modifications that differs from the classical Hebb rule and that can account for both homosynaptic LTD and LTP as well as for heterosynaptic competition and associativity.

  17. Consider long-term care as service alternative.

    PubMed

    Loria, L S

    1987-04-01

    The increasing demand for elderly care services, pressures on inpatient average length of stay and payment levels, and potential financial rewards from providing additional services, makes long-term care look attractive to hospitals. Long-term care, however, is not for every hospital. Before deciding to establish long-term care services, management should examine how the service fits within the hospital's strategic plan. The action plan below provides guidance in evaluating a decision to use hospital facilities for long-term care. Examine how long-term care services fit within the hospital's strategic plan. Study area demographics and competitors to assess the need and supply of long-term care services. Survey the medical staff, consumers and payers to determine attitudes, perceptions and interests regarding long-term care services. Develop a facility plan that identifies areas of excess capacity that can be most easily converted into long-term care with minimal effects on hospital operations. Prepare a financial feasibility analysis of the contribution margin and return on investment attributable to long-term care services. Include an impact analysis on hospital operations. Establish a management task force to develop a detailed implementation plan including assigned individual responsibilities and related timetable. Develop an effective marketing plan designed to generate increased patient market share.

  18. Long-Term Monitoring of Global Climate Forcings and Feedbacks

    NASA Technical Reports Server (NTRS)

    Hansen, J. (Editor); Rossow, W. (Editor); Fung, I. (Editor)

    1993-01-01

    A workshop on Long-Term Monitoring of Global Climate Forcings and Feedbacks was held February 3-4, 1992, at NASA's Goddard Institute for Space Studies to discuss the measurements required to interpret long-term global temperature changes, to critique the proposed contributions of a series of small satellites (Climsat), and to identify needed complementary monitoring. The workshop concluded that long-term (several decades) of continuous monitoring of the major climate forcings and feedbacks is essential for understanding long-term climate change.

  19. Long-term effects of orthodontic treatment on periodontal health.

    PubMed

    Sadowsky, C; BeGole, E A

    1981-08-01

    The periodontal health of a group of ninety-six patients who had received comprehensive fixed-appliance orthodontic treatment during adolescence between 12 and 35 years previously was evaluated. Comparisons were made with a group of 103 adults who were similar with regard to race, sex, age, socioeconomic status, dental awareness, and oral hygiene status but had malocclusions that had not been orthodontically treated. There were no statistically significant differences in the general prevalence of periodontal disease between the two groups. However, more detailed analysis revealed that the orthodontic group had a greater prevalence of mild to moderate periodontal disease in the maxillary posterior and mandibular anterior regions of the mouth, as compared to the control group. The results suggested that orthodontic treatment in adolescence is not a major factor in determining the long-term periodontal health status. No significant amount of either damage or benefit to the periodontal structures could be directly attributed to orthodontic therapy. Conversely, the lack of orthodontic therapy in adolescence does not appear to influence subsequent development or nondevelopment of periodontal disease in adults.

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

    PubMed

    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.

  1. Increased contribution of L-arginine-nitric oxide pathway in aorta of mice lacking the gene for vimentin.

    PubMed

    Zhang, J; Henrion, D; Ebrahimian, T; Benessiano, J; Colucci-Guyon, E; Langa, F; Lévy, B I; Boulanger, C M

    2001-10-01

    Experiments were designed to investigate endothelial function in the aorta of mice lacking the gene for the cytoskeleton protein vimentin (vim -/- ). Rings with and without endothelium from wild-type (vim +/+ ), heterozygous (vim +/- ), and homozygous (vim -/- ) mice were suspended in organ chambers to record of changes in isometric tension. During phenylephrine contraction, acetylcholine evoked comparable endothelium-dependent relaxations in the three groups. In the presence of Nomega-nitro-L-arginine, acetylcholine caused endothelium-dependent contractions, which were greater in vim -/- than in vim +/+ and vim +/- aortas. Indomethacin did not affect relaxation to acetylcholine in vim +/+ or in vim +/-, but it significantly increased the maximal response in vim -/- (67 +/- 7 vs. 102 +/- 4%). Response to acetylcholine in vim -/- aortas was not affected by cyclooxygenase type 2 inhibitor NS-398, the thromboxane receptor antagonist SQ-29,548, or superoxide dismutase. Relaxations to sodium nitroprusside were not different between vim +/+ and vim -/- mice and were not affected by cyclooxygenase inhibition. Cyclic guanosine monophosphate levels, which were increased to a comparable level by acetylcholine in vim +/+ and vim -/-, were augmented by indomethacin in vim -/- aortas but not in vim +/+ aortas. Expression of endothelial nitric oxide synthase was not different between vim +/+ and vim -/- preparations. These results suggest that despite comparable endothelium-dependent responses to acetylcholine, endothelial cells from vim -/- mice release a cyclooxygenase product that compensates the augmented contribution of nitric oxide.

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  3. Comparative Proteomics Analysis Reveals L-Arginine Activates Ethanol Degradation Pathways in HepG2 Cells

    PubMed Central

    Yan, Guokai; Lestari, Retno; Long, Baisheng; Fan, Qiwen; Wang, Zhichang; Guo, Xiaozhen; Yu, Jie; Hu, Jun; Yang, Xingya; Chen, Changqing; Liu, Lu; Li, Xiuzhi; Purnomoadi, Agung; Achmadi, Joelal; Yan, Xianghua

    2016-01-01

    L-Arginine (Arg) is a versatile amino acid that plays crucial roles in a wide range of physiological and pathological processes. In this study, to investigate the alteration induced by Arg supplementation in proteome scale, isobaric tags for relative and absolute quantification (iTRAQ) based proteomic approach was employed to comparatively characterize the differentially expressed proteins between Arg deprivation (Ctrl) and Arg supplementation (+Arg) treated human liver hepatocellular carcinoma (HepG2) cells. A total of 21 proteins were identified as differentially expressed proteins and these 21 proteins were all up-regulated by Arg supplementation. Six amino acid metabolism-related proteins, mostly metabolic enzymes, showed differential expressions. Intriguingly, Ingenuity Pathway Analysis (IPA) based pathway analysis suggested that the three ethanol degradation pathways were significantly altered between Ctrl and +Arg. Western blotting and enzymatic activity assays validated that the key enzymes ADH1C, ALDH1A1, and ALDH2, which are mainly involved in ethanol degradation pathways, were highly differentially expressed, and activated between Ctrl and +Arg in HepG2 cells. Furthermore, 10 mM Arg significantly attenuated the cytotoxicity induced by 100 mM ethanol treatment (P < 0.0001). This study is the first time to reveal that Arg activates ethanol degradation pathways in HepG2 cells. PMID:26983598

  4. N(G)-nitro-L-arginine methyl ester, but not methylene blue, attenuates anaphylactic hypotension in anesthetized mice.

    PubMed

    Takano, Hiromichi; Liu, Wei; Zhao, Zhansheng; Cui, Sen; Zhang, Wei; Shibamoto, Toshishige

    2007-07-01

    To clarify the role of NO in mouse anaphylactic hypotension, effects of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on antigen-induced hypotension and portal hypertension were determined in anesthetized BALB/c mice. Systemic arterial pressure (Psa), central venous pressure (Pcv), and portal venous pressure (Ppv) were directly and simultaneously measured. Mice were first sensitized with ovalbumin, and then the injection of antigen was used to decrease Psa and increase Ppv. Pretreatment with L-NAME (1 mg/kg) attenuated this antigen-induced systemic hypotension, but not the increase in Ppv. The effect of inhibitors of soluble guanylate cyclase on anaphylactic hypotension were studied with either methylene blue (3.0 mg/kg) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10 mg/kg). Neither modulated any antigen-induced changes. Furthermore, methylene blue did not improve systemic hypotension induced by Compound 48/80 (4.5 mg/kg), a mast cell degranulator, which can produce non-immunological anaphylactoid reactions. These data show in anesthetized BALB/c mice that L-NAME attenuated anaphylactic hypotension without affecting portal hypertension. This beneficial effect of L-NAME appears not to depend on the soluble guanylate cyclase pathway.

  5. Hyperargininemia and renal oxidative stress: Prevention by antioxidants and N(G) -nitro-l-arginine methyl ester.

    PubMed

    Delwing-de Lima, Daniela; Delwing-Dal Magro, Débora; Vieira, Cindy Laís Pett; Grola, Gislaine Maria Marestoni; Fischer, Débora Adriana; de Souza Wyse, Angela Terezinha

    2017-01-01

    We investigated the in vitro and in vivo effects of arginine (Arg) on thiobarbituric acid-reactive substances (TBA-RS) and on the activities of catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in renal tissues of rats. We also studied the influence of antioxidants (α-tocopherol plus ascorbic acid) and nitric oxide synthase inhibitor N(G) -nitro-l-arginine methyl ester (l-NAME) on the effects elicited by Arg. Results showed that Arg in vitro (1.5 mM) decreased SOD activity and increased the levels of TBA-RS in the renal medulla. Acute administration of Arg [0.8 g/kg, intraperitoneal injection] decreased CAT activity, increased SOD activity and TBA-RS levels in the renal medulla, and decreased CAT activity in the renal cortex of rats. Most results were prevented by antioxidants and/or l-NAME. Data indicate that Arg causes an oxidative imbalance in the renal tissues studied; however, in the presence of antioxidants and l-NAME, some of these alterations in oxidative stress were prevented.

  6. Simultaneous determination of L-arginine and 12 molecules participating in its metabolic cycle by gradient RP-HPLC method: application to human urine samples.

    PubMed

    Markowski, Piotr; Baranowska, Irena; Baranowski, Jacek

    2007-12-19

    We have developed and described a highly sensitive, accurate and precise reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous determination of L-arginine and 12 molecules participating in its metabolic cycle in human urine samples. After pre-column derivatization with ortho-phthaldialdehyde (OPA) reagent containing 3-mercaptopropionic acid (3MPA), the fluorescent derivatives were separated by a gradient elution and detected by fluorescence measurement at 338 nm (excitation) and 455 nm (emission). L-Arginine (ARG) and its metabolites: L-glutamine (GLN), N(G)-hydroxy-L-arginine (NOHA), L-citrulline (CIT), N(G)-monomethyl-L-arginine (NMMA), L-homoarginine (HARG), asymmetric N(G),N(G)-dimethyl-L-arginine (ADMA), symmetric N(G),N(G')-dimethyl-L-arginine (SDMA), L-ornithine (ORN), putrescine (PUT), agmatine (AGM), spermidine (SPERMD) and spermine (SPERM) were extracted in a cation-exchange solid-phase extraction (SPE) column and after derivatization separated in a Purospher STAR RP-18e analytical column. The calibration curves of analysed compounds are linear within the range of concentration: 45-825, 0.2-15, 16-225, 12-285, 0.1-32, 15-235, 0.1-12, 0.1-12, 10-205, 0.02-12, 0.1-24, 0.01-10 and 0.01-8 nmol mL(-1) for GLN, NOHA, CIT, ARG, NMMA, HARG, ADMA, SDMA, ORN, PUT, AGM, SPERMD and SPERM, respectively. The correlation coefficients are greater than 0.9980. Coefficients of variation are not higher than 6.0% for inter-day precision. The method has been determined or tested for limits of detection and quantification, linearity, precision, accuracy and recovery. All detection parameters of the method demonstrate that it is a reliable and efficient means of the comprehensive determination of ARG and its 12 main metabolites, making this approach suitable for routine clinical applications. The levels of analysed compounds in human urine can be successfully determined using this developed method with no matrix effect.

  7. [Developing the core competencies of long-term care professionals].

    PubMed

    Chen, Huey-Tzy; Lee, Kuang-Ting

    2012-12-01

    Longer average life expectancies and an ageing society have made long-term care an urgent and important issue in Taiwan. Although the implementation of Long-Term Care Ten-year Project four years ago has begun showing success in terms of assessing Taiwan's needs in terms of long-term care services and resources, there has been little forward progress in terms of training, recruiting and maintaining more competent professionals in the long-term care sector. This paper explores the current state of long-term care competency in Taiwan and educational strategies in place to improve the competency of long-term care professionals. Results indicate that the term geriatric competency embraces sub-competencies in direct care, communication, assessment, teamwork, cultural sensitivities and career care competencies. The term long-term care competency embraces the sub-competencies of supervision, management, information technology, resource management, and organizational skill. As a main contributor to effective long-term care, the nursing profession must employ effective strategies to develop competency-based education. Also, the profession must have an adequate supply of competent manpower to effectively respond to Taiwan's aging society.

  8. Long Term Agroecosystem Research in the southern plains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at USDA-ARS’s Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita ...

  9. Short- and Long-Term Consequences of Adolescent Work.

    ERIC Educational Resources Information Center

    Mihalic, Sharon Wofford; Elliott, Delbert

    1997-01-01

    Examines the short- and long-term consequences of working during adolescence. Responses from 1,725 adolescents reveal that the negative short-term effects are in the domains of school, family and friend bonding, beliefs, and substance use. The long-term beneficial effect is that the duration of early work helps employability in adulthood. (GR)

  10. Developmental Dyslexia and Explicit Long-Term Memory

    ERIC Educational Resources Information Center

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  11. Ensuring climate information guides long-term development

    NASA Astrophysics Data System (ADS)

    Jones, Lindsey; Dougill, Andrew; Jones, Richard G.; Steynor, Anna; Watkiss, Paul; Kane, Cheikh; Koelle, Bettina; Moufouma-Okia, Wilfran; Padgham, Jon; Ranger, Nicola; Roux, Jean-Pierre; Suarez, Pablo; Tanner, Thomas; Vincent, Katharine

    2015-09-01

    Many sub-Saharan countries are failing to include climate information in long-term development planning. Ensuring climate-resilient development requires a step change in how medium- to long-term climate information is produced, communicated and utilized in sub-Saharan Africa and elsewhere.

  12. Prediction of Long Term Degradation of Insulating Materials

    DTIC Science & Technology

    2015-05-01

    Physical changes .......................................................................................................... 20 4.2 Thermal performance ...to address the enduring challenge of developing and evaluating the long-term performance of a thermal insula- tion for shelter systems that provides...properties of selected insulation ma- terials based on the differences in thermal conductivity and R-values. 3. Predict the long-term performance of selected

  13. Factors Affecting Long-Term Abstinence from Substances Use

    ERIC Educational Resources Information Center

    Elsheikh, Salah Elgaily

    2008-01-01

    Objective: The purpose of this study is to explore the attitudes of abstainers from drug use that relate to the factors leading to long-term abstinence. Materials and Methods: Cross-sectional study was carried out in Al-Amal Hospital to examine, which attitudes of abstainers related to long-term abstinence. A random survey was conducted on 62…

  14. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  15. 47 CFR 54.303 - Long term support.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... base-level of Long Term Support for 1998, the Administrator shall calculate the difference between the.... (2) To calculate Long Term Support for calendar year 1998, the Administrator shall adjust the base...; and (4) The line port costs in excess of basic analog service pursuant to § 69.130 of this...

  16. Perceptions of control and long-term recovery from rape.

    PubMed

    Regehr, C; Cadell, S; Jansen, K

    1999-01-01

    The relationship between perceptions of control and symptoms of both long-term depression and post-traumatic stress was examined. Enduring beliefs of personal competence and control were found to be associated with lower rates of depression and stress and to be stronger predictors of long-term recovery than were rape-specific attributions. Implications for clinical practice are discussed.

  17. A new image for long-term care.

    PubMed

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  18. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to...

  19. 7 CFR 1773.44 - Long-term debt.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Long-term debt. 1773.44 Section 1773.44 Agriculture... (CONTINUED) POLICY ON AUDITS OF RUS BORROWERS RUS Required Audit Procedures and Documentation § 1773.44 Long-term debt. The CPA's workpapers must document that he/she: (a) Confirmed RUS, FFB, and RTB debt to...

  20. The Effect of Modality on Long-Term Recognition Memory.

    ERIC Educational Resources Information Center

    Dean, Raymond S.; And Others

    1988-01-01

    The effects of visual and auditory modes of input on long-term memory were examined in two experiments, each with 40 and 80 undergraduates, respectively. In both experiments, visual stimulus attributes were a more salient dimension than were auditory features in the long-term encoding and retrieval process. (SLD)

  1. Pediatric Facial Fractures and Potential Long-Term Growth Disturbances

    PubMed Central

    Wheeler, Jonathan; Phillips, John

    2011-01-01

    Fractures of the pediatric craniofacial skeleton can be challenging to manage. The initial injury and subsequent treatment can cause long-term growth disturbances yielding problematic secondary deformities. This review considers the normal growth of the craniofacial skeleton and typical facial fracture presentations in children and discusses the potential long-term sequelae from these injuries and their management. PMID:22379506

  2. A perspective on long-term care for the elderly

    PubMed Central

    Scanlon, William J.

    1988-01-01

    Long-term care represents a significant burden to the approximately 7 million elderly in need, their families, and the Medicaid program. Concerns exist about access, quality, cost, and the distribution of the burden of care. In this article each area is discussed, highlighting the principal issues, identifying the unique aspects that pertain to long-term care, and exploring the implications for research and policy development. Future trends, especially the growth of the elderly population, are expected to affect significantly the provision of long-term care. The considerable uncertainty about how these trends may impact on long-term care is described, and the critical role social choice will play in shaping the future long-term care system is emphasized. PMID:10312975

  3. Environmental Management Long-Term Stewardship Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after the completion of facility cleanup. Long-term stewardship is administered and overseen by the U.S. Department of Energy Environmental Management Office of Science and Technology. This report describes the background of long-term stewardship and gives general guidance about considerations when ownership and/or responsibility of a site should be transferred to a long-term stewardship program. This guidance document will assist the U.S. Department of Energy in: (a) ensuring that the long-term stewardship program leads transition planning with respect to facility and site areas, and (b) describing the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete.

  4. The relationship between interannual and long-term cloud feedbacks

    SciTech Connect

    Zhou, Chen; Zelinka, Mark D.; Dessler, Andrew E.; Klein, Stephen A.

    2015-12-11

    The analyses of Coupled Model Intercomparison Project phase 5 simulations suggest that climate models with more positive cloud feedback in response to interannual climate fluctuations also have more positive cloud feedback in response to long-term global warming. Ensemble mean vertical profiles of cloud change in response to interannual and long-term surface warming are similar, and the ensemble mean cloud feedback is positive on both timescales. However, the average long-term cloud feedback is smaller than the interannual cloud feedback, likely due to differences in surface warming pattern on the two timescales. Low cloud cover (LCC) change in response to interannual and long-term global surface warming is found to be well correlated across models and explains over half of the covariance between interannual and long-term cloud feedback. In conclusion, the intermodel correlation of LCC across timescales likely results from model-specific sensitivities of LCC to sea surface warming.

  5. Osteonecrosis of the Femoral Head in an Adolescent on Long-Term Inhalational Corticosteroids

    PubMed Central

    Ballock, R. Tracy

    2017-01-01

    A relationship between the development of osteonecrosis of the femoral head and systemic corticosteroids has been well established in the literature, particularly in adults. However, the link between osteonecrosis and inhaled corticosteroids is less researched and understood. We report an usual case report of a 10-year-old male who developed ipsilateral femoral head osteonecrosis after long-term inhalational corticosteroid and intermittent short courses of oral steroid usage with a unique presentation and delayed diagnosis. PMID:28337355

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

    PubMed

    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.

  7. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    ERIC Educational Resources Information Center

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  8. Achieving high gene delivery performance with caveolae-mediated endocytosis pathway by (l)-arginine/(l)-histidine co-modified cationic gene carriers.

    PubMed

    Li, Hui; Luo, Ting; Sheng, Ruilong; Sun, Jingjing; Wang, Zhao; Cao, Amin

    2016-12-01

    Developing new amphiphilic polymers with natural product moieties has been regarded as a promising way to achieve biocompatibility and certain biological functions. In prior work, we developed some natural (l)-arginine modified cationic polymers (PAHMAA-Rs) as cationic gene carriers. For the sake of continuing optimize the gene delivery performance, herein, a new series of (l)-arginine and (l)-histidine co-modified cationic poly (ω-aminohexyl methacrylamide)s (PAHMAA-R-H) were synthesized and characterized with (1)H NMR, GPC-SLS and FT-IR. Their proton buffering capacities were studied by acid-base titration assay. pDNA binding affinity and self-assembly properties of the polyplexes were analyzed by agarose gel retardation assay, DLS and AFM, respectively. In vitro cytotoxicity of the PAHMAA-R-H was determined by MTT and LDH assays in H1299 cells, the gene transfection efficacy and intracellular uptake capability were evaluated by luciferase assay and FACS, respectively. Moreover, the endocytosis pathways and intracellular distribution of the polyplexes were investigated by using specific endocytic inhibitors and fluorescent co-localization techniques. The results demonstrated that co-modification of (l)-arginine and (l)-histidine onto the PAHMAA polymer could enhance proton buffering capacity, shield surface charge, decrease cytotoxicity, and improve gene transfection efficiency and serum-compatibility. Moreover, the gene transfection and intracellular uptake behaviors were disclosed strongly rely on the (l)-arginine/(l)-histidine modification ratios. The polyplexes tend to be internalized through caveolae-mediated endocytosis gateway and localized with endosomes/lysosomes in H1299 cells. Notably, among the polymers, the PAHMAA-R18-H6 exhibited remarkable gene delivery efficiency and serum compatibility, which made it promising gene transfection agent for practical application.

  9. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

    PubMed

    Luetic, Krešimir; Sucic, Mario; Vlainic, Josipa; Halle, Zeljka Belosic; Strinic, Dean; Vidovic, Tinka; Luetic, Franka; Marusic, Marinko; Gulic, Sasa; Pavelic, Tatjana Turudic; Kokot, Antonio; Seiwerth, Ranka Serventi; Drmic, Domagoj; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag

    2017-04-01

    We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

  10. Comparative study on the protective role of vitamin C and L-arginine in experimental renal ischemia reperfusion in adult rats

    PubMed Central

    Mohamed, Abd El-Hamid A; Lasheen, Noha N

    2014-01-01

    Ischemia reperfusion (I/R) injury is a main cause of transplanted kidney dysfunction and rejection. Reactive oxygen species (ROS) play a causal role in cellular damage induced by I/R. Antioxidant vitamins and Nitric oxide (NO) were postulated to play renoprotective effects against I/R. This study compares the protective effects of vitamin C with that of the nitric oxide donor, L-arginine, on renal I/R injury in adult rats. The study was performed on 50 adult Wistar rats of both sexes, divided into 5 groups: I: Control group, receive daily intraperitoneal (i.p.) saline for 3 days. II: Renal I/R group, received i.p saline for 3 days and subjected to renal I/R. III: L-arginine Pretreated, 400 mg/kg/day i.p. for 3 days prior to I/R. IV: Vitamin C Pretreated, 500 mg/kg/day i.p. 24 hours prior to I/R. V: combined L-arginine and Vitamin C Pretreated, exposed to Renal I/R group. At the end of the experiment, plasma urea and creatinine were determined. Kidney tissue malondialdehyde (MDA), NO, catalase and superoxide dismutase (SOD) activity were measured and kidneys were examined histologically. Results: I/R group showed significant increase in plasma urea, creatinine, and renal MDA, and a significant decrease in renal catalase with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney section compared to the control group. All the treated groups showed significant decrease in urea, creatinine, and MDA, and a significant increase in catalase with less histopathological changes in kidney sections compared to I/R group. However, significant improvements in urea, MDA, and catalase were found in vitamin C pretreated and combined treated groups than L-arginine pretreated group. Conclusion: Oxidative stress is the primary element involved in renal I/R injury. So, antioxidants play an important renoprotective effects than NO donors. PMID:25349638

  11. The transporter and permeability interactions of asymmetric dimethylarginine (ADMA) and L-arginine with the human blood-brain barrier in vitro.

    PubMed

    Watson, Christopher P; Pazarentzos, Evangelos; Fidanboylu, Mehmet; Padilla, Beatriz; Brown, Rachel; Thomas, Sarah A

    2016-10-01

    The blood-brain barrier (BBB) is a biological firewall that carefully regulates the cerebral microenvironment by acting as a physical, metabolic and transport barrier. This selectively permeable interface was modelled using the immortalised human cerebral microvascular endothelial cell line (hCMEC/D3) to investigate interactions with the cationic amino acid (CAA) L-arginine, the precursor for nitric oxide (NO), and with asymmetric dimethylarginine (ADMA), an endogenously derived analogue of L-arginine that potently inhibits NO production. The transport mechanisms utilised by L-arginine are known but they are not fully understood for ADMA, particularly at the BBB. This is of clinical significance giving the emerging role of ADMA in many brain and cerebrovascular diseases and its potential as a therapeutic target. We discovered that high concentrations of ADMA could induce endothelial dysfunction in the hCMEC/D3s BBB permeability model, leading to an increase in paracellular permeability to the paracellular marker FITC-dextran (40kDa). We also investigated interactions of ADMA with a variety of transport mechanisms, comparing the data with L-arginine interactions. Both molecules are able to utilise the CAA transport system y(+). Furthermore, the expression of CAT-1, the best known protein from this group, was confirmed in the hCMEC/D3s. It is likely that influx systems, such as y(+)L and b(0,+), have an important physiological role in ADMA transport at the BBB. These data are not only important with regards to the brain, but apply to other microvascular endothelia where ADMA is a major area of investigation.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26716991

  14. Production of the amino acids l-glutamate, l-lysine, l-ornithine and l-arginine from arabinose by recombinant Corynebacterium glutamicum.

    PubMed

    Schneider, Jens; Niermann, Karin; Wendisch, Volker F

    2011-07-10

    Amino acid production processes with Corynebacterium glutamicum are based on media containing glucose from starch hydrolysis or fructose and sucrose as present in molasses. Simultaneous utilization of various carbon sources, including glucose, fructose and sucrose, in blends is a typical characteristic of this bacterium. The renewable non-food carbon source arabinose, which is present in hemicellulosic hydrolysates, cannot be utilized by most C. glutamicum strains. Heterologous expression of the araBAD operon from Escherichia coli in the wild-type and in an l-lysine producing strain of C. glutamicum was shown to enable production of l-glutamate and l-lysine, respectively, from arabinose as sole carbon source. l-Ornithine and l-arginine producing strains were constructed and shown to produce l-ornithine and l-arginine from arabinose when araBAD from E. coli was expressed. Moreover, the recombinant strains produced l-glutamate, l-lysine, l-ornithine and l-arginine respectively, from arabinose also when glucose-arabinose blends were used as carbon sources.

  15. New technical approaches in stereotaxic catheterization of cerebral ventriculi: implications for the L-arginine/NO synthase/nitric oxide cascade.

    PubMed

    Manolidis, G; Neamţu, C; Vasincu, D; Jaba, Irina-Maria; Rădăşanu, Oana; Mungiu, O C

    2004-01-01

    In order to study the actions of certain substances at cerebral level, a stereotactic device for ensuring a precise catheterization of points in certain cerebral areas was used. For the operation technique was used a stereotaxic atlas specifically designed for rat brain (G. Paxinos, C. Watson, 1998), which offers all the necessary information for the identification of the trepanation. Stereotaxic implantation of cannules in the brain is useful for microinjecting solutions containing various substances (in amounts of microl), directly and targeted in the anatomical structures of the brain. The technique described can use either metalic or silastic cannules, that have variable lumen (usually for adapting a Hamilton syringe). The cannules can be implanted at cerebroventricular level, having the possibility to target all the cerebral ventricles. The intracerebroventricular (icv) administration of L-arginine induces a significant increase of response latency for mechano-algesic test. The most obvious changes are induced following the administration of the association of L-NAME with L-arginine, situation when is manifested an important increase of the response latency, starting with 5 minutes post-administration and continuing up to 45 minutes determination. The increase is significantly higher compared with the results obtained with L-arginine alone. A similar evolution is registered in the case of the plantar test.

  16. A comparative study on pure, L-arginine and glycine doped ammonium dihydrogen orthophosphate single crystals grown by slow solvent evaporation and temperature-gradient method

    NASA Astrophysics Data System (ADS)

    Pattanaboonmee, N.; Ramasamy, P.; Yimnirun, R.; Manyum, P.

    2011-01-01

    Single crystals of pure, L-arginine and glycine doped ammonium dihydrogen orthophosphate (ADP) were grown by both the slow solvent evaporation method and the temperature-gradient method of Sankaranarayanan-Ramasamy (SR). The metastable zone width for different saturation temperatures of pure glycine and L-arginine added solutions were carried out. The grown crystals were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction (XRD), optical transmission, dielectric constant, dielectric loss, and Vickers microhardness. The DSC and TG curves of the grown crystals indicated that they were stable up to 200 °C. The XRD study confirmed the structure of the grown crystal. The optical transmission analysis revealed that the pure and doped ADP crystals had very high percentage of transmission in the entire visible region. The important optical parameters such as reflectance and extinction coefficients of the grown crystals were calculated. L-arginine and glycine were used as dopants to reduce dielectric constant of ADP. The a.c. resistivity and a.c. conductivity were calculated. Dielectric loss of the doped ADP crystals grown by the SR method is lower than the doped ADP crystals grown by the conventional method. Larger hardness value for the SR method grown crystals confirmed greater crystalline perfection.

  17. Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction.

    PubMed

    Aoki, Hiromitsu; Nagao, Junji; Ueda, Taro; Strong, Jeffry M; Schonlau, Frank; Yu-Jing, Song; Lu, Yan; Horie, Shigeo

    2012-02-01

    A double-blind parallel group comparison design clinical study was conducted in Japanese patients with mild to moderate erectile dysfunction to investigate the efficacy of a supplement containing Pycnogenol® and L-arginine. Subjects were instructed to take a supplement (Pycnogenol® 60 mg/day, L-arginine 690 mg/day and aspartic acid 552 mg/day) or an identical placebo for 8 weeks, and the results were assessed using the five-item erectile domain (IIEF-5) of the International Index of Erectile Function. Additionally, blood biochemistry, urinalysis and salivary testosterone were measured. Eight weeks of supplement intake improved the total score of the IIEF-5. In particular, a marked improvement was observed in 'hardness of erection' and 'satisfaction with sexual intercourse'. A decrease in blood pressure, aspartate transaminase and γ-glutamyl transpeptidase (γ-GTP), and a slight increase in salivary testosterone were observed in the supplement group. No adverse reactions were observed during the study period. In conclusion, Pycnogenol® in combination with L-arginine as a dietary supplement is effective and safe in Japanese patients with mild to moderate erectile dysfunction.

  18. Improvement of seminal quality and sexual function of men with oligoasthenoteratozoospermia syndrome following supplementation with L-arginine and Pycnogenol®.

    PubMed

    Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sadaoka, Yuko; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi; Strong, Jeffry Michael; Rohdewald, Peter

    2015-09-30

    We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol(®) in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol(®)) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol(®) activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol(®) and L-arginine (Edicare(®)) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

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

    PubMed

    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.

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

    PubMed Central

    Fazelian, Siavash; Hoseini, Mostafa; Namazi, Nazli; Heshmati, Javad; Sepidar Kish, Mehdi; Mirfatahi, Maryam; Some Olia, Ahmad Saedi

    2014-01-01

    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 (P<0.05). After adjusting for dietary intake, no significant difference was observed in Fat Mass (FM) and Fat Free Mass (FFM) between two groups (P>0.05). 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. PMID:25364661

  1. Long-Term Stewardship Baseline Report and Transition Guidance

    SciTech Connect

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  2. Depletion of L-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes

    PubMed Central

    García-Navas, Rósula; Munder, Markus; Mollinedo, Faustino

    2012-01-01

    L-arginine (L-Arg) deficiency results in decreased T-cell proliferation and impaired T-cell function. Here we have found that L-Arg depletion inhibited expression of different membrane antigens, including CD247 (CD3ζ), and led to an ER stress response, as well as cell cycle arrest at G0/G1 in both human Jurkat and peripheral blood mitogen-activated T cells, without undergoing apoptosis. By genetic and biochemical approaches, we found that L-Arg depletion also induced autophagy. Deprivation of L-Arg induced EIF2S1 (eIF2α), MAPK8 (JNK), BCL2 (Bcl-2) phosphorylation, and displacement of BECN1 (Beclin 1) binding to BCL2, leading to autophagosome formation. Silencing of ERN1 (IRE1α) prevented the induction of autophagy as well as MAPK8 activation, BCL2 phosphorylation and XBP1 splicing, whereas led T lymphocytes to apoptosis under L-Arg starvation, suggesting that the ERN1-MAPK8 pathway plays a major role in the activation of autophagy following L-Arg depletion. Autophagy was required for survival of T lymphocytes in the absence of L-Arg, and resulted in a reversible process. Replenishment of L-Arg made T lymphocytes to regain the normal cell cycle profile and proliferate, whereas autophagy was inhibited. Inhibition of autophagy by ERN1, BECN1 and ATG7 silencing, or by pharmacological inhibitors, promoted cell death of T lymphocytes incubated in the absence of L-Arg. Our data indicate for the first time that depletion of L-Arg in T lymphocytes leads to a reversible response that preserves T lymphocytes through ER stress and autophagy, while remaining arrested at G0/G1. Our data also show that the L-Arg depletion-induced ER stress response could lead to apoptosis when autophagy is blocked. PMID:22874569

  3. Effects of intragastric L-arginine administration on proximal stomach tone under basal conditions and after an intragastric diet.

    PubMed

    Savoye, Guillaume; Jemaa, Yassine; Mosni, Grégory; Savoye-Collet, Céline; Morcamp, Paola; Déchelotte, Pierre; Bouin, Mickael; Denis, Philippe; Ducrotté, Philippe

    2006-12-01

    Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment.L-Arg administration was associated with significantly higher increases in barostat bag volumes at both dosages, 30 g (117+/-16 ml) and 15 g (67+/-15 ml), compared to placebo (46+/-11 ml; P < 0.05). In response to the polymeric diet the 30-g L-Arg challenge was associated with a smaller increase in intrabag volume, whereas postinfusion final volumes did not differ in the three treatment conditions. Antral areas were not different at any time of measurement among the three challenges. Bloating and diarrhea were observed after 30-g L-Arg administration in five subjects of eight. Short-term L-Arg administration was able to induce proximal stomach relaxation that allowed a secondary response to enteral feeding only at the 15-g dosage. This 15-g dosage was as well tolerated as the placebo and was associated with no significant changes in gastric emptying patterns.

  4. Regulatory role for L-arginine in the utilization of amino acids by pig small-intestinal bacteria.

    PubMed

    Dai, Zhao-Lai; Li, Xi-Long; Xi, Peng-Bin; Zhang, Jing; Wu, Guoyao; Zhu, Wei-Yun

    2012-07-01

    We recently reported that bacteria from the pig small intestine rapidly utilize and metabolize amino acids (AA). This study investigated the effect of L-arginine on the utilization of AA by pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the pig small intestine. Bacteria were incubated at 37°C for 3 h in anaerobic AA media containing 0-5 mmol/L of arginine to determine the effect of arginine on the bacterial utilization of AA. Amino acids in the medium plus cell extracts were analyzed by high-performance liquid chromatography. Results indicated concentration-dependent increases in the bacterial utilization of arginine and altered fluxes of arginine into ornithine and citrulline in the bacteria. Net glutamine utilization increased in pure bacterial strains with increased concentrations of arginine. With the addition of arginine, net utilization of threonine, glycine, phenylalanine and branched-chain AA increased (P<0.05) in Streptococcus sp. and Klebsiella sp., but decreased in E. coli. Net utilization of lysine, threonine, isoleucine, leucine, glycine and alanine by jejunal or ileal mixed bacteria decreased (P<0.05) with the addition of arginine. Complete utilization of asparagine, aspartate and serine were observed in pig small-intestinal bacteria after 3 h of incubation. Overall, the addition of arginine affected the metabolism of the arginine-family of AA and the serine- and aspartate-family of AA in small-intestinal bacteria and reduced the utilization of most AA in ileal mixed bacteria. These novel findings indicate that arginine exerts its beneficial effects on swine nutrition partially by regulating AA utilization and metabolism in the small-intestinal microbiota.

  5. Cardiovascular Action of Insulin in Health and Disease: Endothelial L-Arginine Transport and Cardiac Voltage-Dependent Potassium Channels

    PubMed Central

    Dubó, Sebastián; Gallegos, David; Cabrera, Lissette; Sobrevia, Luis; Zúñiga, Leandro; González, Marcelo

    2016-01-01

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

  6. Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle.

    PubMed

    Tan, Bie; Yin, Yulong; Liu, Zhiqiang; Tang, Wenjie; Xu, Haijun; Kong, Xiangfeng; Li, Xinguo; Yao, Kang; Gu, Wanting; Smith, Stephen B; Wu, Guoyao

    2011-05-01

    Obesity is a major health crisis worldwide and new treatments are needed to fight this epidemic. Using the swine model, we recently reported that dietary L-arginine (Arg) supplementation promotes muscle gain and reduces body-fat accretion. The present study tested the hypothesis that Arg regulates expression of key genes involved in lipid metabolism in skeletal muscle and white adipose tissue. Sixteen 110-day-old barrows were fed for 60 days a corn- and soybean-meal-based diet supplemented with 1.0% Arg or 2.05% L-alanine (isonitrogenous control). Blood samples, longissimus dorsi muscle and overlying subcutaneous adipose tissue were obtained from 170-day-old pigs for biochemical studies. Serum concentrations of leptin, alanine and glutamine were lower, but those for Arg and proline were higher in Arg-supplemented pigs than in control pigs. The percentage of oleic acid was higher but that of stearic acid and linoleic acid was lower in muscle of Arg-supplemented pigs, compared with control pigs. Dietary Arg supplementation increased mRNA levels for fatty acid synthase in muscle, while decreasing those for lipoprotein lipase, glucose transporter-4, and acetyl-coenzyme A carboxylase-α in adipose tissue. Additionally, mRNA levels for hormone sensitive lipase were higher in adipose tissue of Arg-supplemented pigs compared with control pigs. These results indicate that Arg differentially regulates expression of fat-metabolic genes in skeletal muscle and white adipose tissue, therefore favoring lipogenesis in muscle but lipolysis in adipose tissue. Our novel findings provide a biochemical basis for explaining the beneficial effect of Arg in improving the metabolic profile in mammals (including obese humans).

  7. Space ventures and society long-term perspectives

    NASA Technical Reports Server (NTRS)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  8. Medical care evaluation studies in long-term care facilities.

    PubMed

    Zimmer, J G

    1979-02-01

    This report describes the selection, design, conduct, analysis, and application of medical care evaluation studies in long-term care facilities (skilled nursing homes) in a regional program in the Rochester region of upstate New York. Eight examples are presented to highlight methodologic approaches and problems. They are classified under four general headings: Administration Audits, Diagnosis-specific Studies, Care Modality-specific Studies, and General Outcome Indicators. The implementation of results and recommendations from the studies is discussed and an application of "tracer" methodology for assessing the components of care activities in long-term facilities is described. Problems and challenges in long-term quality care are outlined.

  9. Long-term outcome of lung transplantation in previous intravenous drug users with talc lung granulomatosis.

    PubMed

    Weinkauf, J G; Puttagunta, L; Nador, R; Jackson, K; LaBranche, K; Kapasi, A; Mullen, J; Modry, D L; Stewart, K C; Thakrar, M; Doucette, K; Lien, D C

    2013-01-01

    Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.

  10. L-arginine

    MedlinePlus

    ... tolerance in people taking nitroglycerin for chest pain (angina pectoris). Leg pain associated with poor blood flow (peripheral ... For chest pain associated with coronary artery disease (angina pectoris): 3-6 grams three times per day for ...

  11. The modulation of NMDA receptors and L-arginine/nitric oxide pathway is implicated in the anti-immobility effect of creatine in the tail suspension test.

    PubMed

    Cunha, Mauricio P; Pazini, Francis L; Ludka, Fabiana K; Rosa, Julia M; Oliveira, Ágatha; Budni, Josiane; Ramos-Hryb, Ana B; Lieberknecht, Vicente; Bettio, Luis E B; Martín-de-Saavedra, Maria D; López, Manuela G; Tasca, Carla I; Rodrigues, Ana Lúcia S

    2015-04-01

    The modulation of N-methyl-D-aspartate receptor (NMDAR) and L-arginine/nitric oxide (NO) pathway is a therapeutic strategy for treating depression and neurologic disorders that involves excitotoxicity. Literature data have reported that creatine exhibits antidepressant and neuroprotective effects, but the implication of NMDAR and L-arginine/nitric oxide (NO) pathway in these effects is not established. This study evaluated the influence of pharmacological agents that modulate NMDAR/L-arginine-NO pathway in the anti-immobility effect of creatine in the tail suspension test (TST) in mice. The NOx levels and cellular viability in hippocampal and cerebrocortical slices of creatine-treated mice were also evaluated. The anti-immobility effect of creatine (10 mg/kg, po) in the TST was abolished by NMDA (0.1 pmol/mouse, icv), D-serine (30 µg/mouse, icv, glycine-site NMDAR agonist), arcaine (1 mg/kg, ip, polyamine site NMDAR antagonist), L-arginine (750 mg/kg, ip, NO precursor), SNAP (25 μg/mouse, icv, NO donor), L-NAME (175 mg/kg, ip, non-selective NOS inhibitor) or 7-nitroindazole (50 mg/kg, ip, neuronal NOS inhibitor), but not by DNQX (2.5 µg/mouse, icv, AMPA receptor antagonist). The combined administration of sub-effective doses of creatine (0.01 mg/kg, po) and NMDAR antagonists MK-801 (0.001 mg/kg, po) or ketamine (0.1 mg/kg, ip) reduced immobility time in the TST. Creatine (10 mg/kg, po) increased cellular viability in hippocampal and cerebrocortical slices and enhanced hippocampal and cerebrocortical NO x levels, an effect potentiated by L-arginine or SNAP and abolished by 7-nitroindazole or L-NAME. In conclusion, the anti-immobility effect of creatine in the TST involves NMDAR inhibition and enhancement of NO levels accompanied by an increase in neural viability.

  12. Long Term 1 Enhanced Surface Water Treatment Rule Documents

    EPA Pesticide Factsheets

    The Long Term 1 Enhanced Surface Water Treatment Rule (LT1ESWTR) builds on the requirements of the Surface Water Treatment Rule and specifies treatment requirements to address Cryptosporidium m and other microbial contaminants in public water systems.

  13. Long-term storage of bionanodevices by freezing and lyophilization.

    PubMed

    Seetharam, Raviraja; Wada, Yuuko; Ramachandran, Sujatha; Hess, Henry; Satir, Peter

    2006-09-01

    Successful long-term storage of a "smart dust" device integrating biomolecular motors and complex protein assemblies has been demonstrated using freezing or lyophilization, which implies that fabrication and application can be separated even for complex bionanodevices.

  14. Examining Long-Term Global Climate Change on the Web.

    ERIC Educational Resources Information Center

    Huntoon, Jacqueline E.; Ridky, Robert K.

    2002-01-01

    Describes a web-based, inquiry-oriented activity that enables students to examine long-term global climate change. Supports instruction in other topics such as population growth. (Contains 34 references.) (DDR)

  15. Long-term Outcomes of Childhood Onset Nephrotic Syndrome

    PubMed Central

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated. PMID:27252935

  16. Long-term Outcomes of Childhood Onset Nephrotic Syndrome.

    PubMed

    Hjorten, Rebecca; Anwar, Zohra; Reidy, Kimberly Jean

    2016-01-01

    There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under-recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated.

  17. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    SciTech Connect

    T. Haney R. VanHorn

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  18. Long-term pharmacological treatment of generalized anxiety disorder.

    PubMed

    Mahe, V; Balogh, A

    2000-03-01

    Generalized anxiety disorder (GAD) is one of the most common anxiety disorders and has a poor prognosis, although it is often thought to be a minor complaint. This disorder has a chronic course of 5-15 years and longer. Long-term treatment with the commonly used benzodiazepines is controversial because of concerns over tolerance and dependence. We performed a thorough search of the literature for clinical trials of a duration of over 2 months conducted in patients with generalized anxiety disorder in order to identify any successful long-term treatment of this disorder. Only eight long-term reports of studies conducted in well-defined homogeneous groups of patients diagnosed with generalized anxiety disorder were found with the methodology of these studies presenting a number of limiting factors. The results are inconclusive and no reference drug could be identified. In addition, an adequate evaluation of the long-term treatment of GAD has not yet been performed.

  19. Earth's Long-Term Warming Trend, 1880-2015

    NASA Video Gallery

    This visualization illustrates Earth’s long-term warming trend, showing temperature changes from 1880 to 2015 as a rolling five-year average. Orange colors represent temperatures that are warmer th...

  20. Long-term monitoring for nanomedicine implants and drugs

    NASA Astrophysics Data System (ADS)

    Kendall, Michaela; Lynch, Iseult

    2016-03-01

    Increasing globalization means that traditional occupational epidemiological approaches may no longer apply, suggesting a need for an alternative model to assess the long-term impact of nanomaterial exposure on health.

  1. The Long Term Agroecosystem Research Network - Shared research strategy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agriculture faces tremendous challenges in meeting multiple societal goals, including a safe and plentiful food supply; climate change adaptation and mitigation; supplying sources of bioenergy; improving water, air, and soil quality; and maintaining biodiversity. The Long Term Agroecosystem Research...

  2. Biogeochemistry: Long-term effects of permafrost thaw

    NASA Astrophysics Data System (ADS)

    Zona, Donatella

    2016-09-01

    Carbon emissions from the Arctic tundra could increase drastically as global warming thaws permafrost. Clues now obtained about the long-term effects of such thawing on carbon dioxide emissions highlight the need for more data.

  3. Lead and Copper Rule Long-Term Revisions

    EPA Pesticide Factsheets

    The goal for the Lead and Copper Rule (LCR) Long-Term Revisions is to improve public health protection provided by the by making substantive changes based on topics that were identified in the 2004 National Review.

  4. The market for long-term care services.

    PubMed

    Grabowski, David C

    2008-01-01

    Although a large literature has established the importance of market and regulatory forces within the long-term care sector, current research in this field is limited by a series of data, measurement, and methodological issues. This paper provides a comprehensive review of these issues with an emphasis on identifying initiatives that will increase the volume and quality of long-term care research. Recommendations include: the construction of standard measures of long-term care market boundaries, the broader dissemination of market and regulatory data, the linkage of survey-based data with market measures, the encouragement of further market-based studies of noninstitutional long-term care settings, and the standardization of Medicaid cost data.

  5. Finance issue brief: long-term care insurance.

    PubMed

    Mintz, E

    1999-08-03

    States are turning their attention to long-term care insurance, spurred by a 1996 federal law and an increasingly urgent need for more options to finance the care of their rapidly growing elderly populations.

  6. Long-term care: a substantive factor in financial planning.

    PubMed

    Willis, D A

    2000-01-01

    More than 50 percent of women will enter a nursing home at some point in their lives. About one-third of men living to age 65 will also need nursing home care. Planning for long-term care is even more important since Medicare covers very little of the cost of such care. The Indiana Partnership Plan is one program designed to help fund the long-term care costs while allowing individuals protect other financial assets.

  7. Long-term effects of sludge application to land

    SciTech Connect

    Geertsema, W.S. ); Knocke, W.R.; Novak, J.T.; Dove, D. . Dept. of Civil Engineering)

    1994-11-01

    The purpose of this study was to evaluate the long-term environmental effects of applying alum sludge to land. Investigations at the original field site included soil analysis, soil water monitoring, groundwater monitoring, and analysis of tissues from pine needles. No long-term (30 months) effects were observed, and the authors conclude that alum coagulant sludges can be applied to forest lands at loading rates of at least 1.5 to 2.5% by dry weight without adverse effect.

  8. The Long-Term Behavior of Known & Suspected Novae

    NASA Astrophysics Data System (ADS)

    Pagnotta, A.

    2017-03-01

    The long-term evolution of classical novae is poorly understood. I discuss here an in-progress project designed to better understand the post-eruption behavior of novae and test the Hibernation theory of nova evolution. The project has two main parts: (1) a modern survey of Galactic nova magnitudes, and (2) construction of long-term light curves using primarily archival photographic plates.

  9. Long-term Morphological Modeling at Coastal Inlets

    DTIC Science & Technology

    2015-05-15

    The CMS consists of an integrated numerical modeling system for simulating wave, current, water levels, sediment transport and morphology change ...In order to quantify the physical effects of long-term, regional climactic changes in the environment, numerical morphodynamic models must be able...components of long-term, regional climactic changes in the environment. Numerical morphodynamic models must be able to reproduce the known generic

  10. Maintaining Engagement in Long-term Interventions with Relational Agents

    PubMed Central

    Bickmore, Timothy; Schulman, Daniel; Yin, Langxuan

    2011-01-01

    We discuss issues in designing virtual humans for applications which require long-term voluntary use, and the problem of maintaining engagement with users over time. Concepts and theories related to engagement from a variety of disciplines are reviewed. We describe a platform for conducting studies into long-term interactions between humans and virtual agents, and present the results of two longitudinal randomized controlled experiments in which the effect of manipulations of agent behavior on user engagement was assessed. PMID:21318052

  11. Fast and long term lipid droplet tracking with CARS microscopy.

    PubMed

    Jüngst, Christian; Winterhalder, Martin J; Zumbusch, Andreas

    2011-06-01

    Photobleaching of organic fluorophores commonly used in fluorescence microscopy puts a limit to the number of images which can be acquired. Label-free imaging techniques therefore offer advantages both for rapid image acquisition and for long-term observations. CARS microscopy is a label-free imaging technique offering molecule specific contrast. Here we demonstrate that CARS microscopy allows video-rate tracking of intracellular transport of lipid droplets, but also continuous long-term observation of cells over several hours.

  12. Influenza in long-term care facilities: preventable, detectable, treatable.

    PubMed

    Mossad, Sherif B

    2009-09-01

    Influenza in long-term care facilities is an ever more challenging problem. Vaccination of residents and health care workers is the most important preventive measure. Although vaccine efficacy has been questioned, the preponderance of data favors vaccination. Antiviral resistance complicates postexposure chemoprophylaxis and treatment. Factors that limit the choice of antiviral agents in this patient population include limited vaccine supplies and impaired dexterity and confusion in long-term care residents.

  13. Motivating the paraprofessional in long-term care.

    PubMed

    Vance, A; Davidhizar, R

    1997-06-01

    Motivating the paraprofessional employee in the long-term care setting is one of the biggest challenges facing health care supervisors. Unlike their counterparts in industry, whose work may produce tangible results and rewards, long-term care professionals often must face patients who show little or no change over time. Supervisors must have understanding and knowledge of motivational techniques that will involve and challenge paraprofessionals.

  14. Planning long-term vegetation studies at landscape scales

    USGS Publications Warehouse

    Stohlgren, Thomas J.

    1995-01-01

    Long-term ecological research is receiving more attention now than ever before. Two recent books, Long-term Studies in Ecology: Approaches and Alternatives, edited by Gene Likens (1989), and Long-term Ecological Research: An International Perspective, edited by Paul Risser (1991), prompt the question, “Why are these books so thin?” Except for data from paleoecological, retrospective studies (see below), there are exceptionally few long-term data sets in terrestrial ecology (Strayer et al. 1986; Tilman 1989; this volume). In a sample of 749 papers published in Ecology, Tilman (1989) found that only 1.7% of the studies lasted at least five field seasons. Only one chapter in each of the review books dealt specifically with expanding both the temporal and the spatial scales of ecological research (Berkowitz et al. 1989; Magnuson et al. 1991). Judging by the growing number of landscape-scale long-term studies, however, such as the Long-Term Ecological Research (LTER) Program (Callahan 1991), the U.S. Environmental Protection Agency’s Environmental Monitoring and Assessment Program (EMAP; Palmer et al. 1991), the U.S. Army’s Land Condition-Trend Analysis (LCTA) Program (Diersing et al. 1992), and various agencies’ global change research programs (CEES 1993), there is a growing interest to expand ecological research both temporally and spatially.

  15. Salivary caries risk factors in long-term event-free survivors of pediatric malignant diseases.

    PubMed

    Dens, F L; Boute, P; Vinckier, F; Declerck, D

    1996-01-01

    In this study we demonstrated that caries prevalence and Plaque Index in long-term event-free pediatric oncology patients are related to Streptococcus mutans, Lactobacillus counts and buffer capacity obtained by chairside saliva tests. The scores showed a significant correlation between the microbiological findings and caries experience in both groups. The results were compared with a control group. A similarity in the results was found between the study and control groups. In a subgroup consisting of children who were diagnosed with cancer maximum two years before oral examinations, no significant differences with a control group was noticed. In this study we did not find any evidence of long-term effects on the studied salivary caries risk factors in children who are long-term event-free after cytotoxic treatment. Chairside tests seem to be useful in this patient group: they provide us information which can contribute to the determination of the individual caries risk, and help to motivate the patient and health care workers to maintain optimal oral hygiene.

  16. Long-term treatment with tetrahydrobiopterin in phenylketonuria: treatment strategies and prediction of long-term responders.

    PubMed

    Hennermann, Julia B; Roloff, Sylvia; Gebauer, Christine; Vetter, Barbara; von Arnim-Baas, Annabel; Mönch, Eberhard

    2012-11-01

    Tetrahydrobiopterin (BH4) responsive phenylketonuria has been described more than 10 years ago. However, criteria for the identification of long-term BH4 responsive patients are not yet established. 116 patients with phenylketonuria, aged 4-18 years, were screened for potential long-term BH4 responsiveness by at least two of the following criteria: positive neonatal BH4 loading test, putative BH4 responsive genotype, and/or milder phenotype. Patients had to be on permanent dietary treatment. 23 patients fulfilled these criteria and were tested for long-term BH4 responsiveness: 18/23 were long-term BH4 responsive, 5/23 were not. On long-term BH4 treatment over a period of 48 ± 27 months in a dose of 14.9 ± 3.3mg/kg/day phenylalanine tolerance was increased from 452 ± 201 mg/day to 1593 ± 647 mg/day, corresponding to a mean increase of 1141 ± 528 mg/day. Dietary phenylalanine intake was increased stepwise according to a clear defined protocol. In 8/18 patients, diet was completely liberalized; 10/18 patients still received phenylalanine-free amino acid formula with 0.63 ± 0.23 g/kg/day. The most predictive value for long-term BH4 responsiveness was the combination of pretreatment phenylalanine of < 1200 μmol/L, pretreatment phenylalanine/tyrosine ratio of <15, phenylalanine/tyrosine ratio of <15 on treatment, phenylalanine tolerance of >20mg/kg/day at age 3 years, positive neonatal BH4 loading, and at least one putative BH4 responsive mutation (p = 0.00024). Our data show that long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. A clear defined protocol is necessary to install long-term BH4 treatment.

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

    PubMed

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

    2010-02-01

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

  18. The L-Arginine Transporter Solute Carrier Family 7 Member 2 Mediates the Immunopathogenesis of Attaching and Effacing Bacteria

    PubMed Central

    Singh, Kshipra; Verriere, Thomas G.; Coburn, Lori A.; Asim, Mohammad; Allaman, Margaret M.; Hardbower, Dana M.; Delgado, Alberto G.; Vallance, Bruce A.; Gobert, Alain P.; Wilson, Keith T.

    2016-01-01

    Solute carrier family 7 member 2 (SLC7A2) is an inducible transporter of the semi-essential amino acid L-arginine (L-Arg), which has been implicated in immune responses to pathogens. We assessed the role of SLC7A2 in murine infection with Citrobacter rodentium, an attaching and effacing enteric pathogen that causes colitis. Induction of SLC7A2 was upregulated in colitis tissues, and localized predominantly to colonic epithelial cells. Compared to wild-type mice, Slc7a2–/–mice infected with C. rodentium had improved survival and decreased weight loss, colon weight, and histologic injury; this was associated with decreased colonic macrophages, dendritic cells, granulocytes, and Th1 and Th17 cells. In infected Slc7a2–/–mice, there were decreased levels of the proinflammatory cytokines G-CSF, TNF-α, IL-1α, IL-1β, and the chemokines CXCL1, CCL2, CCL3, CCL4, CXCL2, and CCL5. In bone marrow chimeras, the recipient genotype drove the colitis phenotype, indicative of the importance of epithelial, rather than myeloid SLC7A2. Mice lacking Slc7a2 exhibited reduced adherence of C. rodentium to the colonic epithelium and decreased expression of Talin-1, a focal adhesion protein involved in the attachment of the bacterium. The importance of SLC7A2 and Talin-1 in the intimate attachment of C. rodentium and induction of inflammatory response was confirmed in vitro, using conditionally-immortalized young adult mouse colon (YAMC) cells with shRNA knockdown of Slc7a2 or Tln1. Inhibition of L-Arg uptake with the competitive inhibitor, L-lysine (L-Lys), also prevented attachment of C. rodentium and chemokine expression. L-Lys and siRNA knockdown confirmed the role of L-Arg and SLC7A2 in human Caco-2 cells co-cultured with enteropathogenic Escherichia coli. Overexpression of SLC7A2 in human embryonic kidney cells increased bacterial adherence and chemokine expression. Taken together, our data indicate that C. rodentium enhances its own pathogenicity by inducing the expression

  19. A Novel Role for SIRT-1 in L-Arginine Protection against STZ Induced Myocardial Fibrosis in Rats

    PubMed Central

    Rizk, Sherine M.; El-Maraghy, Shohda A.; Nassar, Noha N.

    2014-01-01

    Background L-arginine (L-ARG) effectively protects against diabetic impediments. In addition, silent information regulator (SIRT-1) activators are emerging as a new clinical concept in treating diabetic complications. Accordingly, this study aimed at delineating a role for SIRT-1 in mediating L-ARG protection against streptozotocin (STZ) induced myocardial fibrosis. Methods Male Wistar rats were allocated into five groups; (i) normal control rats received 0.1 M sodium citrate buffer (pH 4.5); (ii) STZ at the dose of 60 mg/kg dissolved in 0.1 M sodium citrate buffer (pH 4.5); (iii) STZ + sirtinol (Stnl; specific inhibitor of SIRT-1; 2 mg/Kg, i.p.); (iv) STZ + L-ARG given in drinking water (2.25%) or (v) STZ + L-ARG + Stnl. Results L-ARG increased myocardial SIRT-1 expression as well as its protein content. The former finding was paralleled by L-ARG induced reduction in myocardial fibrotic area compared to STZ animals evidenced histopathologically. The reduction in the fibrotic area was accompanied by a decline in fibrotic markers as evident by a decrease in expression of collagen-1 along with reductions in myocardial TGF-β, fibronectin, CTGF and BNP expression together with a decrease in TGF-β and hydroxyproline contents. Moreover, L-ARG increased MMP-2 expression in addition to its protein content while decreasing expression of PAI-1. Finally, L-ARG protected against myocardial cellular death by reduction in NFκ-B mRNA as well as TNF-α level in association with decline in Casp-3 and FAS expressions andCasp-3protein content in addition to reduction of FAS positive cells. However, co-administration of L-ARG and Stnl diminished the protective effect of L-ARG against STZ induced myocardial fibrosis. Conclusion Collectively, these findings associate a role for SIRT-1 in L-ARG defense against diabetic cardiac fibrosis via equilibrating the balance between profibrotic and antifibrotic mediators. PMID:25501750

  20. Exogenous L-arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis-diuresis relationship.

    PubMed

    Das, Satarupa; Mattson, David L

    2014-04-01

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

  1. Long-term treatment of major depressive disorder with paroxetine.

    PubMed

    Duboff, E A

    1993-12-01

    Recurrent unipolar depression is a common, but undertreated disorder. Many patients require long-term maintenance therapy, and full doses of antidepressant agents may be preferred for the prevention of relapse. We report results of a 1-year, multicenter, open-label study of paroxetine (10 to 50 mg/day) in 433 patients with major depressive disorder, with additional data from 110 patients who entered a long-term extension of the study. The primary measures of efficacy were the Hamilton Rating Scale for Depression (HAM-D) total and Clinical Global Impression (CGI) severity of illness scores. During the first 6 weeks of therapy, the mean HAM-D total declined approximately 50% (from 27.9 to 13.5), with continued improvement, at an attenuated rate, throughout the first year. At the end of 1 year, the mean HAM-D total was 6.9. Similarly, the CGI severity of illness score declined from 4.6 at baseline to 2.8 at week 6 and to 1.7 at the end of 1 year. Remission was maintained in the population that entered the long-term extension, with mean HAM-D total and CGI severity of illness scores of 6.4 and 1.8, respectively, after 2.5 years, and 4.2 and 1.3 after 4 years. The most common adverse events reported during long-term treatment with paroxetine were somnolence, nausea, headache, and sweating. Pharmacokinetic analysis showed no clear correlation between the concentrations of paroxetine in plasma and either clinical efficacy or tolerability. There was no increased drug accumulation during long-term treatment. Side effects tended to occur early during therapy; and no new side effects emerged during the long-term extension. These results suggest that paroxetine is effective and well tolerated in the long-term treatment of depression.

  2. Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions

    PubMed Central

    Tain, You-Lin; Lee, Chien-Te; Huang, Li-Tung

    2014-01-01

    Maternal malnutrition can elicit gene expression leading to fetal programming. l-citrulline (CIT) can be converted to l-arginine to generate nitric oxide (NO). We examined whether maternal CIT supplementation can prevent NG-nitro-l-arginine-methyl ester (l-NAME, NO synthase inhibitor)-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq) technology. Pregnant Sprague-Dawley rats received l-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% l-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, l-NAME, and l-NAME + CIT. l-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in l-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP) and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification. PMID:25517031

  3. Child maltreatment: pathway to chronic and long-term conditions?

    PubMed

    Taylor, Julie; Bradbury-Jones, Caroline; Lazenbatt, Anne; Soliman, Francesca

    2016-09-01

    The manifesto Start Well, Live Better by the UK Faculty of Public Health (Start Well, Live Better-A Manifesto for the Public's Health. London: UK Faculty of Public Health, 2014) sets out 12 compelling priorities for the protection of people's health. The focus of this document is preventative, calling for a comprehensive strategy to target a wide-ranging set of challenges to public health; however, it fails to mention child maltreatment and its negative impact on long-term health outcomes. In this article, we explore the long-term negative consequences of child maltreatment and how these can be conceptually aligned with four different characteristics of long-term health conditions. We suggest that situating child maltreatment within a long-term conditions framework could have significant advantages and implications for practice, policy and research, by strengthening a commitment across disciplines to apply evidence-based principles linked with policy and evaluation and recognizing the chronic effects of maltreatment to concentrate public, professional and government awareness of the extent and impact of the issue. We argue that a public health approach is the most effective way of focusing preventative efforts on the long-term sequelae of child maltreatment and to foster cooperation in promoting children's rights to grow and develop in a safe and caring environment free from violence and abuse.

  4. Characteristics of Long-Term Survivors of Epithelial Ovarian Cancer

    PubMed Central

    Cress, Rosemary D.; Chen, Yingjia S.; Morris, Cyllene R.; Petersen, Megan; Leiserowitz, Gary S.

    2015-01-01

    Objective To identify characteristics associated with long-term survival forepithelial ovarian cancer patients using the California Cancer Registry. Methods A descriptive analysis of survival of all California residents diagnosed with epithelial ovarian cancer between 1994 and 2001 was conducted using patients identified through the cancer registry with follow up through 2011. Characteristics of the patients who survived more than 10 years (long-term survivors) were compared to three other cohorts: patients who survived less than 2 years, those who survived at least 2 but no more than 5 years, and those who survived at least 5 but no more than 10 years. Results A total of 3,582 out of 11,541 (31% CI=30.2%, 31.8%) of the patients survived more than 10 years. Younger age, early stage, low-grade, and non-serous histology were significant predictors of long-term survival, but long-term survivors also included women with high-risk cancer. Conclusion Long-term survival is not unusual in patients with epithelial ovarian cancer, even in those with high-risk disease. Many of the prognostic factors are well known, but it remains to be determined why some patients with advanced stage high-grade cancers survive longer than others with the same histology. These findings are important for patient counseling. PMID:26244529

  5. Method for Water Management Considering Long-term Probabilistic Forecasts

    NASA Astrophysics Data System (ADS)

    Hwang, J.; Kang, J.; Suh, A. S.

    2015-12-01

    This research is aimed at predicting the monthly inflow of the Andong-dam basin in South Korea using long-term probabilistic forecasts to apply long-term forecasts to water management. Forecasted Cumulative Distribution Functions (CDFs) of monthly precipitation are plotted by combining the range of monthly precipitation based on proper Probability Density Function (PDF) in past data with probabilistic forecasts in each category. Ensembles of inflow are estimated by entering generated ensembles of precipitation based on the CDFs into the 'abcd' water budget model. The bias and RMSE between averages in past data and observed inflow are compared to them in forecasted ensembles. In our results, the bias and RMSE of average precipitation in the forecasted ensemble are bigger than in past data, whereas the average inflow in the forecasted ensemble is smaller than in past data. This result could be used for reference data to apply long-term forecasts to water management, because of the limit in the number of forecasted data for verification and differences between the Andong-dam basin and the forecasted regions. This research has significance by suggesting a method of applying probabilistic information in climate variables from long-term forecasts to water management in Korea. Original data of a climate model, which produces long-term probabilistic forecasts should be verified directly as input data of a water budget model in the future, so that a more scientific response in water management against uncertainty of climate change could be reached.

  6. Common Calibration Source for Monitoring Long-term Ozone Trends

    NASA Technical Reports Server (NTRS)

    Kowalewski, Matthew

    2004-01-01

    Accurate long-term satellite measurements are crucial for monitoring the recovery of the ozone layer. The slow pace of the recovery and limited lifetimes of satellite monitoring instruments demands that datasets from multiple observation systems be combined to provide the long-term accuracy needed. A fundamental component of accurately monitoring long-term trends is the calibration of these various instruments. NASA s Radiometric Calibration and Development Facility at the Goddard Space Flight Center has provided resources to minimize calibration biases between multiple instruments through the use of a common calibration source and standardized procedures traceable to national standards. The Facility s 50 cm barium sulfate integrating sphere has been used as a common calibration source for both US and international satellite instruments, including the Total Ozone Mapping Spectrometer (TOMS), Solar Backscatter Ultraviolet 2 (SBUV/2) instruments, Shuttle SBUV (SSBUV), Ozone Mapping Instrument (OMI), Global Ozone Monitoring Experiment (GOME) (ESA), Scanning Imaging SpectroMeter for Atmospheric ChartographY (SCIAMACHY) (ESA), and others. We will discuss the advantages of using a common calibration source and its effects on long-term ozone data sets. In addition, sphere calibration results from various instruments will be presented to demonstrate the accuracy of the long-term characterization of the source itself.

  7. Long-Term Stewardship Program Science and Technology Requirements

    SciTech Connect

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the