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Effects of Long-term Oral Administration of L-Arginine on the Rat Erectile Response  

Microsoft Academic Search

PurposeNitric oxide (NO), the neurotransmitter responsible for mediating penile erection in the rat, is synthesized from L arginine by nitric oxide synthase (NOS) in a reaction blocked by L-NAME (N-Omega-nitro-L-arginine methyl ester). To determine whether dietary supplementation of L-arginine can stimulate penile erection and whether ancillary pathways for penile erection may exist, a series of experiments were conducted in the

J. A. Moody; D. Vernet; S. Laidlaw; J. Rajfer; N. F. Gonzalez-Cadavid



Long-term L-Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function in Humans  

Microsoft Academic Search

Background—Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodi- lating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of L-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive

Amir Lerman; John C. Burnett; Stuart T. Higano; Linda J. McKinley; David R. Holmes


Long-term dietary L-arginine supplementation attenuates proteinuria and focal glomerulosclerosis in experimental chronic renal transplant failure.  


Glomerular endothelial nitric oxide synthase expression is decreased in humans during acute rejection and chronic renal transplant failure (CRTF). This may contribute to vascular damage through changes in the renal hemodynamics and enhanced endothelial adhesion of leukocytes and platelets. Dietary supplementation of L-arginine may increase endothelial NO production, thereby protecting the vascular wall and improving renal hemodynamics. We tested the hypothesis that long-term L-arginine supplementation attenuates the development of CRTF in an experimental model for renal transplantation. In the Fisher 344 to Lewis rat model for renal transplantation, renal function and histology of untreated rats was compared with rats receiving L-arginine in the drinking water (10g/L), starting 2 days before transplantation. Every 4 weeks systolic blood pressure was measured and serum and urine were collected for measurement of nitrite and nitrate (NO(x)), creatinine, and proteinuria. At 34 weeks the histological renal damage was assessed by scoring focal glomerulosclerosis and measurement of alpha-smooth muscle actin (alpha-SMA) expression. Urinary NO(x) was significantly increased in treated animals. Proteinuria was significantly lower in L-arginine-treated animals from week 24 onward (p<0.05). Plasma creatinine and creatinine clearance did not differ between the groups. The focal and segmental glomerulosclerosis (FGS) score (max 400) at week 34 was also significantly lower in treated rats arbitrary U (20+/-21 vs 61+/-67 arbitrary U; p<0.05). The expression of alpha-SMA was lower in L-arginine-treated rats than in untreated rats (1.93+/-0.8% area surface vs 3.64+/-2.5% area surface). In conclusion, in this experimental model for CRTF, L-arginine administration significantly reduced FGS and proteinuria, without affecting renal function. Our data suggest that dietary L-arginine supplementation attenuates progression of CRTF and may therefore be an additional therapeutic option in human renal allograft recipients. PMID:12586542

Albrecht, Ester W J A; van Goor, Harry; Smit-van Oosten, Annemieke; Stegeman, Coen A



Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure  

Microsoft Academic Search

Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure.BackgroundCardiovascular disease is a major cause of mortality amongst patients with chronic renal failure (CRF). L-arginine has been used to improve endothelial function by increasing nitric oxide (NO) bioavailability and in animal models this in turn has attenuated the progression of atherosclerosis. We examined whether dietary L-arginine supplementation

Katy J. Bennett-Richards; Mia Kattenhorn; Ann E. Donald; Gillian R. Oakley; Zac Varghese; K. Richard Bruckdorfer; John E. Deanfield; Lesley Rees



Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production  

Microsoft Academic Search

Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g\\/liter water) and captopril (15 mg\\/liter water) was studied in 5\\/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg\\/liter

Ishmail Ashab; Gary Peer; Miriam Blum; Yoram Wollman; Tamara Chernihovsky; Avi Hassner; Doron Schwartz; Shaltiel Cabili; Donald Silverberg; Adrian Iaina



The pharmacodynamics of L-arginine.  


L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes called NO synthases (NOSs). In the brain, NO acts as a neurotransmitter; in the immune system, it acts as a mediator of host defense; and in the cardiovascular system, it mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous, antiatherogenic molecule. About 5 g of L-arginine are ingested each day in a normal Western diet. Plasma levels of L-arginine are not significantly reduced in most diseases, except in end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or dietary (oral) administration of relatively large doses of L-arginine has been shown to result in enhanced NO formation in individuals with impaired endothelial function at baseline. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. However, in other trials, L-arginine was not beneficial, and in a recent study, the authors reported higher mortality for participants receiving L-arginine than for those receiving placebo. Recently, it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-Arginine metabolism by NOS, may determine an individual's response to L-arginine supplementation. L-Arginine appears to exert no effect in individuals with low ADMA levels, whereas in those with high levels, L-arginine restores the L-arginine/ADMA ratio to normal and, thereby, normalizes endothelial function. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Doses of 3-8 g/d appear to be safe and not to cause acute pharmacologic effects in humans. PMID:24755570

Böger, Rainer H



Protective Effect of Oral L -arginine Supplementation on Cyclosporine Induced Nephropathy in Rats  

Microsoft Academic Search

Background: One of the major adverse effects of long term cyclosporine A (CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide (NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. Aim: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage.

Meltem Kuru?; Mukaddes E?refo?lu; Aysun Bay; Feral Öztürk



Effects of oral L-arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic rats.  


This study was carried out to elucidate the role of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) in preeclampsia development, and to investigate the effect of L-arginine supplementation in rats. Preeclampsia was induced in pregnant rats using a stress model. L-arginine was administered orally and ADMA, urinary nitrate, and protein levels were measured on the 20th day of pregnancy. Compared with the group of rats that are normally pregnant, the levels of blood pressure (BP), protein excretion, and ADMA were significantly increased in preeclampsia which returned to normal levels following the supplementation of L-arginine. Both group of rats had similar urine nitrate levels. Arginine-ADMA-NO pathway is affected in preeclampsia. L-arginine supplementation decreased hypertension (HT), proteinuria, and ADMA levels indicating that taking L-arginine may be beneficial in preeclampsia treatment. PMID:18521818

Altun, Zekiye Sultan; Uysal, Sezer; Guner, Gul; Yilmaz, Osman; Posaci, Cemal



Effect of oral l-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries  

Microsoft Academic Search

Thirteen hypertensive patients with microvascular angina were studied before and after receiving oral l-arginine (4 weeks, 2 g, 3 times daily). l-arginine significantly improved angina class, systolic blood pressure at rest, and quality of life. Maximal forearm blood flow, plasma l-arginine, l-arginine:asymmetric dimethyl arginine ratio, and cyclic guanylate monophosphate increased significantly after treatment. In medically treated hypertensive patients with micro-vascular

Altin Palloshi; Gabriele Fragasso; PierMarco Piatti; Lucilla D. Monti; Emanuela Setola; Giampiero Valsecchi; Elena Galluccio; Sergio L. Chierchia; Alberto Margonato



Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling  

PubMed Central

L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells.

Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong



Oral L-arginine before resistance exercise blunts growth hormone in strength trained males.  


Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 ± 4 y; body mass: 81.4 ± 9.0 kg; height: 179.4 ± 6.9 cm; and training experience: 6.3 ± 3.4 y) participated in a randomized double-blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest-recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 ± 368.7 vs. placebo = 487.9± 482.0 min·ng·mL1, p < .05). L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop. PMID:24225560

Forbes, Scott C; Harber, Vicki; Bell, Gordon J



Long-Term Outcome of Individuals Treated With Oral Insulin  

PubMed Central

OBJECTIVE To evaluate the long-term intervention effects of oral insulin on the development of type 1 diabetes and to assess the rate of progression to type 1 diabetes before and after oral insulin treatment was stopped in the Diabetes Prevention Trial–Type 1 (DPT-1). RESEARCH DESIGN AND METHODS The follow-up included subjects who participated in the early intervention of oral insulin (1994–2003) to prevent or delay type 1 diabetes. A telephone survey was conducted in 2009 to determine whether diabetes had been diagnosed and, if not, an oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), and autoantibody levels were obtained on all subjects who agreed to participate. RESULTS Of 372 subjects randomized, 97 developed type 1 diabetes before follow-up; 75% of the remaining 275 subjects were contacted. In the interim, 77 subjects had been diagnosed with type 1 diabetes and 54 of the remainder have had an OGTT; 10 of these were diagnosed with type 1 diabetes, subsequently. Among individuals meeting the original criteria for insulin autoantibodies (IAAs) (?80 nU/mL), the overall benefit of oral insulin remained significant (P = 0.05). However, the hazard rate in this group increased (from 6.4% [95% CI 4.5–9.1] to 10.0% [7.1–14.1]) after cessation of therapy, which approximated the rate of individuals treated with placebo (10.2% [7.1–14.6]). CONCLUSIONS Overall, the oral insulin treatment effect in individuals with confirmed IAA ?80 nU/mL appeared to be maintained with additional follow-up; however, once therapy stopped, the rate of developing diabetes in the oral insulin group increased to a rate similar to that in the placebo group.

Vehik, Kendra; Cuthbertson, David; Ruhlig, Holly; Schatz, Desmond A.; Peakman, Mark; Krischer, Jeffrey P.



Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation  

Microsoft Academic Search

OBJECTIVESThe aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF).BACKGROUNDEndothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise.METHODSForty patients with severe CHF (left ventricular ejection fraction 19 ± 9%) were randomized

Rainer Hambrecht; Lutz Hilbrich; Sandra Erbs; Stephan Gielen; Eduard Fiehn; Nina Schoene; Gerhard Schuler





... L-arginine with ribonucleic acid (RNA) and eicosapentaenoic acid (EPA) before surgery or afterwards seems to help reduce the recovery time, reduce the number of infections, and improve wound healing after surgery. ...


Clinical and radiological assessment of effects of long-term corticosteroid therapy on oral health  

PubMed Central

Background: Corticosteroids (Cs) are used widely for their anti-inflammatory and immunosuppressive properties. They have the potential to cause dramatic improvement as well as produce equally dramatic adverse effects. The clinical misuse like over prescription of the drug should be avoided. Long-term administration may cause many adverse effects leading to impaired oral health. Oral health is usually not considered during management of patients on long-term corticosteroid therapy. The aim of this study was to assess the oral health status and radiological changes in the jaw bones of the patients under long-term corticosteroid therapy. Materials and Methods: Oral health of 100 patients under long-term corticosteroid therapy with a minimum of 3 months duration was compared with sex- and age-matched 100 healthy controls. The clinical examination included complete examination of the mouth and periodontal status. Radiographic evaluation of bone with the help of intra oral periapical radiograph and digital orthopantomograph and levels of serum calcium, alkaline phosphatase, and random blood sugar were assessed. ‘Chi-square test’, ‘Kolmogorov-Smirnov test’ and ‘Mann-Whitney U test’ were used for statistical analysis. P > 0.05 was considered significant. Results: Patients on steroids exhibited significantly higher levels of candidiasis and clinical attachment loss of the periodontal ligament, probing pocket depth. Bone density was significantly lower in the study group than that in the control group. Random blood glucose was significantly higher and significant lower levels of calcium were observed in patients on steroids. Conclusion: Long-term use of Cs may affect oral health adversely leading to candidiasis as well as impair bone metabolism leading to a considerable decrease in the mandibular bone mineral density.

Beeraka, Swapna Sridevi; Natarajan, Kannan; Patil, Rajendra; Manne, Rakesh Kumar; Prathi, Venkata Sarath; Kolaparthi, Venkata Suneel Kumar




Microsoft Academic Search

Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg\\/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of



Long-term effectiveness against cholera of oral killed whole-cell vaccine produced in Vietnam  

Microsoft Academic Search

We assessed the long-term protection afforded by a killed whole-cell oral cholera vaccine produced in Vietnam. A mass immunization of children and adults with the killed whole-cell oral cholera vaccine was undertaken in half of the communes of Hue, Vietnam, in 1998; the remaining communes were immunized in 2000. No cholera was observed in Hue until 2003, when an outbreak

Vu Dinh Thiem; Jacqueline L. Deen; Lorenz von Seidlein; Do Gia Canh; Dang Duc Anh; Jin-Kyung Park; Mohammad Ali; M. Carolina Danovaro-Holliday; Nguyen Dinh Son; Nguyen Thai Hoa; Jan Holmgren; John D. Clemens



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

PubMed Central

Objective To study the effect of oral administration of a nitric oxide (NO) donor l-arginine (l-Arg), a NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. Methods Male Wistar rats received per os l-Arg (800 mg/kg) or l-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (l-Arg(IR1), l-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (l-Arg(IR8), l-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. Results After 1 hr of reperfusion serum NO concentration was elevated in IR1 and l-Arg(IR1) groups compared with group C but not in l-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in l-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, l-Arg(IR8), l-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. Conclusions The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of l-Arg but not after administration of l-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os supplementation of l-Arg or Allo in intestinal I/R.

Yanni, Amalia E; Margaritis, Eleutherios; Liarakos, Nikolaos; Pantopoulou, Alkisti; Poulakou, Maria; Kostakis, Maria; Perrea, Despoina; Kostakis, Alkis



Left ventricular diastolic dysfunction in patients with bronchial asthma with long-term oral ? 2-adrenoceptor agonists  

Microsoft Academic Search

Background Long-term administration of oral ?2-adrenergic receptor agonists (?2-AG) in patients with bronchial asthma (BA) causes disastrous events such as sudden death and heart attack. However, long-term effects of ?2-AG on cardiac function have not been previously quantified. Methods Seventy-four patients with BA with regular long-term use of oral ?2-AG (group A) and 69 patients with BA without ?2- AG

Osamu Hirono; Isao Kubota; Osamu Minamihaba; Kaniz Fatema; Shuichi Kato; Hidenori Nakamura; Hitonobu Tomoike



Oral health champions in long-term care facilities-a pilot study.  


This preintervention/postintervention pilot study examined impact of onsite support by a dental hygiene champion (DHC) on oral health and quality of life (QOL) of elderly residents in three long-term care facilities (LTCFs) in Arkansas. Oral health and oral health-related QOL were operationalized using the Oral Health Assessment Tool (OHAT) and Geriatric Oral Health Assessment Index (GOHAI), respectively. CNAs in Facility A received standardized oral health education/materials with onsite DHC support. Facility B received education/materials only. Facility C served as control. Data analyses included Wilcoxon-signed rank tests (OHAT) and repeated measures ANOVA (GOHAI) (p ? .05). OHAT postintervention data in Facility A showed significant improvements in three measured areas (tongue health, denture status, and oral cleanliness); in Facility B, one area (tongue health); and none in Facility C. No significant differences were found in GOHAI scores across facilities. Findings suggest that the presence of DHCs in LTCFs may positively impact the oral health of CNA-assisted residents. PMID:25039379

Amerine, Carol; Boyd, Linda; Bowen, Denise M; Neill, Karen; Johnson, Tara; Peterson, Teri



Formyl- L-arginine monohydrate  

NASA Astrophysics Data System (ADS)

A new compound N?-formyl- L-arginine +(H 2N) 2CNH(CH 2) 3CH(HN(HCO))COO - with zwitter-ionic structure has been found out in the system L-arginine + HCOOH + H 2O. The title compound crystallizes in monoclinic system (space group P2 1) as monohydrate. Crystal structure has been determined by single crystal X-ray diffraction method and FTIR ATR, FT Raman spectra are reported. Dehydration process has been studied.

Karapetyan, H. A.; Antipin, M. Yu.; Sukiasyan, R. P.; Petrosyan, A. M.



[Management of major bleeding complications in patients on long-term treatment with oral anticoagulants].  


The new direct oral anticoagulants directly targeting thrombin (factor IIa) or factor-Xa, are currently used for the treatment of deep venous thrombosis and pulmonary embolism (rivaroxaban, Xarelto) or for the prevention of systemic embolism in non-valvular atrial fibrillation (rivaroxaban; dabigatran, Pradaxa; Apixaban, Eliquis). Given their ease of use, it is expected that these drugs would be widely used in such long-term indications. Beyond their effectiveness, these treatments remain anticoagulant drugs, potentially responsible for bleeding complications, and specific measures should be defined in case of occurrence of such complications. PMID:24624626

Pernod, Gilles



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

PubMed Central

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

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



Growth hormone in postmenopausal women after long-term oral estrogen replacement therapy.  


Studies of estrogen effects on growth hormone (GH) and its pulsatile release in postmenopausal women have typically utilized estrogen replacement therapy (ERT) of relatively short duration (days to weeks). The purpose of this study was to compare GH measures from healthy postmenopausal women who were on oral ERT for 3 years or more (n = 24; mean ERT duration = 16.1 years) with women not on ERT (NERT; n = 40). Blood samples were drawn remotely every 20 min for 24 h and then analyzed for mean 24-h GH, mean GH during sleep, and mean 24-h insulin-like growth factor-I (IGF-I). GH peak analyses were also performed. Mean 24-h GH and GH during sleep were significantly higher and IGF-I was significantly lower in ERT women compared with NERT women. In addition, use of long-term ERT was associated with more GH peaks relative to women not on ERT, but no change in GH peak amplitude or area. GH was not related to age in either group. GH was strongly and negatively correlated with measures of adiposity in NERT women but not in ERT women. In conclusion, long-term oral ERT is associated with increased circulating GH and decreased IGF-I levels, even after many years of treatment. PMID:9520907

Moe, K E; Prinz, P N; Larsen, L H; Vitiello, M V; Reed, S O; Merriam, G R



Long-term bone retention of C-14 following oral administration of C-14-xylose  

SciTech Connect

Oral administration of C-14-labeled xylose followed by measurement of C-14 activity in the breath has become a clinically useful test for diagnosis of small bowel bacterial overgrowth. However, accurate biodistribution and radiation dosimetry information was not available in the literature, so the true radiation exposure of the human subjects was not known. The purpose of this study was to determine the actual biodistribution data for orally administered C-14-xylose. A series of rats were given the material orally and sacrificed at various ages, up to 1 month after dosing. Tissues and fluids were solubilized and counted by liquid scintillation counting. Exhaled C-14-carbon dioxide was measured by trapping the gas in ethanolamine. Approximately two-thirds of the administered dose was absorbed from the GI tract and eventually appeared in the breath and urine. Much of the dose was not found in the major organs within the first day; it was presumed to be in the fatty tissue or muscle, which were not sampled. After most of the C-14 had disappeared from the GI and urinary tract, however, the bone retained a significant amount of radioactivity: approximately 5-6% of the administered dose was found in bone at one week, and remained at one month. These findings suggest that radiation exposure to the skeleton is long-term, much greater in magnitude than previously estimated, and suggests that the value of the test should be reevaluated in the light of the long-term radiation burden to the skeleton, especially in young patients.

Knight, L.C.; Siegel, J.; Fisher, R.S.; Malmud, L.S.



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

PubMed Central

Background. Many Long-Term Care (LTC) institutionalized patients are the most frail and functionally dependent among the geriatric population and have significant oral health disparities.They often suffer from dental neglect due to limited access to appropriate professional dental care. These patients have chronic health situations and are treated with medications, which increase their risk of oral diseases. Despite the growth in elderly population in Israel, there is insufficient data regarding their oral health status and treatment needs. Objective. To describe the oral health status of the LTC hospitalized adults in a geriatric and psychiatric hospital in Israel. Methods. Data was recorded from LTC hospitalized adults with a physical and/or mental disabilities in a cross-sectional research design, which included general health anamnesis and clinical oral examination. Variables included gender, medicines, oral hygiene (OH), using dentures, number of caries lesions and residual teeth. Univariate analyses included Pearson ?2 and t-test analyses. Multivariate analyses included logistic and linear regressions while the outcome variables were categorical OH index and number of carious cavitations, number of residual teeth and carious teeth percentage. Results. 153 participants were included in the study with a mean age of 65.03 ± 18.67 years. 31.3% of the patients were edentulous, and only 14% had partial or full dentures. Females had a significantly higher number of caries cavitation than males (P = 0.044). The number of caries cavitation was higher among patients with poor OH (P < 0.001) and when taking Clonazepam (P = 0.018). Number of residual teeth was higher in the fair OH group (P < 0.001). Carious teeth percentage was higher among the poor OH group (P < 0.001).

Yavnai, Nirit; Zini, Avi



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


Background. Many Long-Term Care (LTC) institutionalized patients are the most frail and functionally dependent among the geriatric population and have significant oral health disparities.They often suffer from dental neglect due to limited access to appropriate professional dental care. These patients have chronic health situations and are treated with medications, which increase their risk of oral diseases. Despite the growth in elderly population in Israel, there is insufficient data regarding their oral health status and treatment needs. Objective. To describe the oral health status of the LTC hospitalized adults in a geriatric and psychiatric hospital in Israel. Methods. Data was recorded from LTC hospitalized adults with a physical and/or mental disabilities in a cross-sectional research design, which included general health anamnesis and clinical oral examination. Variables included gender, medicines, oral hygiene (OH), using dentures, number of caries lesions and residual teeth. Univariate analyses included Pearson ? (2) and t-test analyses. Multivariate analyses included logistic and linear regressions while the outcome variables were categorical OH index and number of carious cavitations, number of residual teeth and carious teeth percentage. Results. 153 participants were included in the study with a mean age of 65.03 ± 18.67 years. 31.3% of the patients were edentulous, and only 14% had partial or full dentures. Females had a significantly higher number of caries cavitation than males (P = 0.044). The number of caries cavitation was higher among patients with poor OH (P < 0.001) and when taking Clonazepam (P = 0.018). Number of residual teeth was higher in the fair OH group (P < 0.001). Carious teeth percentage was higher among the poor OH group (P < 0.001). PMID:24949240

Bilder, Leon; Yavnai, Nirit; Zini, Avi



Long term results of sentinel lymph node biopsy in early oral squamous cell carcinoma.  


The objective of the study was to evaluate the long term results of the sentinel node (SN) biopsy technique in the management of the clinically negative (N0) neck in patients with early oral squamous cell carcinoma (T1-T2). Patients with positive SN underwent neck dissection. A sentinel lymph node (SLN) biopsy was performed on 31 consecutive patients. Six of the 31 patients were upstaged by the results of the SLN biopsy. The SLN biopsy allowed the identification of node metastasis in 100% of the cases with a sensitivity of 100%, specificity of 100%, and negative predictive value of 100%. There was a mean follow-up of 59 months. The neck control rate was 100% in the SLN negative group and two SLN positive patients developed subsequent neck disease (neck control rate of 88%). One SLN patient presented at the follow-up with a second primary tumor, 18 months later treated successfully by chemoradiotherapy. The overall survival rate was 100% in both groups. The promising reported short-term results have been sustained by long term follow-up. Patients with negative SLN achieved an excellent neck control rate. The neck control rate in SN negative patients was superior to that in SLN positive patients, but not statistically different. PMID:23836993

Dequanter, Didier; Shahla, Mohammad; Paulus, Pascal; Lothaire, Philippe



Long term results of sentinel lymph node biopsy in early oral squamous cell carcinoma  

PubMed Central

The objective of the study was to evaluate the long term results of the sentinel node (SN) biopsy technique in the management of the clinically negative (N0) neck in patients with early oral squamous cell carcinoma (T1–T2). Patients with positive SN underwent neck dissection. A sentinel lymph node (SLN) biopsy was performed on 31 consecutive patients. Six of the 31 patients were upstaged by the results of the SLN biopsy. The SLN biopsy allowed the identification of node metastasis in 100% of the cases with a sensitivity of 100%, specificity of 100%, and negative predictive value of 100%. There was a mean follow-up of 59 months. The neck control rate was 100% in the SLN negative group and two SLN positive patients developed subsequent neck disease (neck control rate of 88%). One SLN patient presented at the follow-up with a second primary tumor, 18 months later treated successfully by chemoradiotherapy. The overall survival rate was 100% in both groups. The promising reported short-term results have been sustained by long term follow-up. Patients with negative SLN achieved an excellent neck control rate. The neck control rate in SN negative patients was superior to that in SLN positive patients, but not statistically different.

Dequanter, Didier; Shahla, Mohammad; Paulus, Pascal; Lothaire, Philippe



Colonization of the oral cavity by Candida species: risk factors in long-term geriatric care.  


The population of elderly people in hospitals for long-term geriatric care presents many risk factors for nosocomial infection by Candida species. The aim of this work was to reduce the risk of C. albicans nosocomial infections starting from colonization of the oral cavity. The population of concern was the patients in long-stay geriatrics units; a sample of 110 people was selected by drawing lots. The clinical and biological parameters of each patient included in the study were recorded. The oral cavity was colonized by Candida spp in 67% of cases. The distribution of the strains showed that C. albicans was the most frequently identified strain, followed by C. glabrata; of the 73 patients with at least one strain of Candida spp., 47 had a clinically diagnosed candidiasis (64.4%). The wearing of dentures was not statistically linked with the development of oral candidiasis. Detecting which patients have been colonized, identifying the risk factors and applying preventive measures should reduce the probability of elderly people falling into the vicious circle of infection-malnutrition-immune-depression. PMID:12816366

Grimoud, Anne M; Marty, Nicole; Bocquet, Hélène; Andrieu, Sandrine; Lodter, Jean P; Chabanon, Gérard



Long-term oral sensitivity and feeding skills of low-risk pre-term infants.  


This study examined the oral sensitivity and feeding skills of low-risk pre-term infants at 11-17 months corrected age. Twenty pre-term infants (PT) born between 32 and 37 weeks at birth without any medical comorbidities were assessed. All of this PT group received supplemental nasogastric (NG) tube feeds during their birth-stay in hospital. A matched control group of 10 healthy full-term infants (FT) was also assessed. Oral sensitivity and feeding skills were assessed during a typical mealtime using the Royal Children's Hospital Oral Sensitivity Checklist (OSC) and the Pre-Speech Assessment Scale (PSAS). Results demonstrated that, at 11-17 months corrected age, the PT group displayed significantly more behaviours suggestive of altered oral sensitivity and facial defensiveness, and a trend of more delayed feeding development than the FT group. Further, results demonstrated that, relative to the FT group, pre-term infants who received greater than 3 weeks of NG feeding (PT>3NG) displayed significantly more facial defensive behaviour, and displayed significant delays across more aspects of their feeding development than pre-term infants who received less than 2 weeks of NG feeding (PT<2NG). The information from this preliminary study suggests that low-risk pre-term infants, particularly those who receive supplemental NG feeding for greater than 3 weeks, may be at risk for displaying long-term altered oral sensitivity and facial defensiveness, as well as feeding delays. These observations warrant further investigation on this topic. PMID:14729160

Dodrill, Pamela; McMahon, Sandra; Ward, Elizabeth; Weir, Kelly; Donovan, Tim; Riddle, Bena



Treatment of oral infections prior to heart valve surgery does not improve long-term survival.  


The objective was to evaluate the importance of preoperative elimination of oral infections and oral health for survival after heart valve surgery In a group of patients (n=149; treatment group, GP group), oral health was examined and dental treatment was performed 3-6 months prior to heart valve surgery. In a second group (n=103; control group, SP group), oral health was examined postoperatively, but patients did not receive dental treatment prior to surgery. Sixteen years after heart valve surgery was performed, morbidity endpoint data were obtained. Differences in survival between the two groups and the influence of differences in oral health were analyzed. Fewer patients survived in the study group (37%) compared with the control group (45%). Mean survival was 122.9 months in the GP group compared with 143.3 months in the SP group, including time to death and those alive at the endpoint (p=0.018). A positive relationship was found between the number of teeth and survival, with RR = 0.98 (95% CI 0962-0.996 (p=0.016)).The deaths from heart valve disease were 18% in the GP group and 7% in the SP group (chi2=3.65, df=1, p=0.56). At the long-term follow-up,the results of the present study show,that it was not possible to demonstrate that dental treatment before heart valve surgery improved survival. Therefore, the need for extensive dental treatment prior to heart valve surgery may be reconsidered. PMID:21827014

Bratel, John; Kennergren, Charles; Dernevik, Leif; Hakeberg, Magnus



No increased risk of infection for long-term sex partners of people with HPV-related oral cancers

Spouses and long-term partners of patients with mouth and throat cancers related to infection with the human papilloma virus (HPV) appear to have no increased prevalence of oral HPV infections, according to results of a multicenter, pilot study led by investigators from Johns Hopkins (home of the Sidney Kimmel Comprehensive Cancer Center). The study’s results suggest that long-term couples need not change their sexual practices, say the scientists.


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


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 oral sodium bicarbonate at the dose of 1 gram thrice daily has no significant effect on nutritional status of HD patients. PMID:17409769

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



Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir.  


Congenital cytomegalovirus infection is the most common cause of nonhereditary sensorineural hearing loss and an important cause of psychomotor retardation. Earlier studies showed that 6-weeks' treatment with ganciclovir, starting in the neonatal period, prevented hearing deterioration at 6 months, but in one-fifth of the infants, the effect was not sustained at age 12 months. The aim of this preliminary retrospective study was to investigate the effectiveness and safety of long-term treatment with ganciclovir/valganciclovir for congenital cytomegalovirus infection. Twenty-three infants with culture-proven symptomatic congenital cytomegalovirus infection were treated with ganciclovir for 6 weeks followed by oral valganciclovir to age 12 months. Audiometry was performed at least three times in the first year, in addition to physical examination including neurological and developmental assessment. At age >or=1 year, hearing was normal in 76% of affected ears compared to baseline (54%). In 25 normal ears at birth no deterioration was found at >or=1 year. These results were significantly better than reported in a historical control group of similar infants treated for 6 weeks only (P= 0.001). Viral load monitoring demonstrated sustained virological response. Four of the children (18%) had mental retardation. The main side effect of treatment was transient neutropenia. In conclusion, prolonged therapy of symptomatic congenital CMV infection with intravenous ganciclovir followed by oral valganciclovir is safe, and it appears to lead to a better auditory outcome than short-term treatment. PMID:20232081

Amir, Jacob; Wolf, Dana G; Levy, Itzhak



Long term oral anticoagulant therapy with warfarin: experience with local patient population in kuwait.  


Warfarin (Coumadin) continues to remain the mainstay of oral anticoagulant therapy (OACT) for thromboprophylaxis for both venous thromboembolic disease (VTD) and cardiac indications. However it needs careful monitoring because of its narrow window of target activity level, interaction with numerous medications and food items, caution for use in patients with co-morbidities like hepatic and renal impairment and bleeding lesions and the risk of major hemorrhage. A large part of its success and safety requires the patients own understanding and participation in its control. In a retrospective study on 153 patients on long term OACT with warfarin, we have analyzed the influence of various personal characteristics of the local patient population like age, gender, nationality, education and financial status, family size, family style, manner of drug administration and number of other medications prescribed for co-morbidities. Ability to achieve consistently efficacious target level of anti coagulant activity is adversely affected by older age, female gender, lower education status, larger family size, joint family setting, dependence on domestic servants to administer warfarin and larger number of other medications taken for co-morbidities. Thirty-seven patients were identified from such vulnerable personal characteristics and assigned to a separate anticoagulant therapy control clinic with specific arrangements for stricter control. This group of patients was studied prospectively for 18 months. Significant improvement was apparent on comparison of their performance before and after assignment to the separate clinic. PMID:24839365

El Ghousain, Husam E; Thomas, Mathew; Varghese, Sunny Joseph; Hegazi, Mohamed O; Kumar, Ramesh



Plasma free captopril concentrations during short and long term treatment with oral captopril for heart failure.  

PubMed Central

Plasma free captopril concentrations and haemodynamic response to captopril were studied in 20 patients with severe chronic heart failure. A 25 mg oral dose of captopril produced a 36% reduction in systemic vascular resistance, with individual responses varying from 13% to 64%. Mean systemic pressure fell by 20% and cardiac output rose 28%. The absorption of captopril was rapid. Peak plasma free captopril concentration occurred at 45 minutes after the dose and was followed by a smaller second peak. Peak plasma free captopril concentrations varied more than 20-fold but did not correlate with the maximal reduction in systemic vascular resistance. Elimination half life was seven hours. Fourteen patients were restudied after 1-2 months of captopril treatment and 12 showed symptomatic benefit. There was a sustained improvement in haemodynamic state and in non-invasive indices of myocardial function. During long term treatment the predose plasma free captopril concentration correlated well with dosage, but steady state captopril concentrations did not show a significant relation with haemodynamic response. On a dosage regimen of 25-50 mg three times daily the morning predose plasma free captopril concentration and plasma renin activity were relatively low and suggested that maximal inhibition of the renin-angiotensin system was not maintained throughout the dosage interval.

Shaw, T R; Duncan, F M; Williams, B C; Crichton, E; Thomson, S A; Davis, J R; Rademaker, M; Edwards, C R



Quantitative imaging of arsenic and its species in goat following long term oral exposure.  


Severity of arsenic toxicity was reported to vary depending on its species. The present study reflects the status of different species of arsenic in goat following long-term exposure of arsenic leading to hepatic damage. The experiment was conducted with six black Bengal goats, which were administered with sodium arsenite orally at a dose rate of 2 mgkg(-1) daily for 84 days. Faeces, urine, hair and blood samples were collected from those animals at 14 days interval. Excretion of total arsenic was reduced from 56 days onwards through both faeces and urine indicating higher accumulation of arsenic in body. The speciation study revealed that urinary arsenic was mainly of organic type, whereas hair accumulated almost equal proportion of arsenite, arsenate and organo arsenicals. Goats excreted high proportion of organo arsenicals through faeces possibly due to hepatobiliary secretion of organo arsenic into the gut. Significantly elevated serum alanine aminotransferase and aspartate aminotransferase activities (p<0.05) along with histopathological changes in liver indicated hepatotoxicity. The arsenite fraction increased and organic proportion decreased in urine as the time progressed, which indicates that arsenite gets methylated in liver of goat. The study thus alluded that the toxicity of arsenic would aggravate if the animals were exposed for long time as the hepatotoxicity progressed resulting in decreased methylation and formation of organo arsenicals and decreased excretions through urine. PMID:22497900

Patra, Pabitra Hriday; Bandyopadhyay, Samiran; Kumar, Rakesh; Datta, Bakul Kumar; Maji, Chinmoy; Biswas, Suman; Dash, Jeevan Ranjan; Sar, Tapas Kumar; Sarkar, Samar; Manna, Sanjib K; Chakraborty, Animesh Kumar; Mandal, Tapan Kumar



Dietary l-Arginine Supplementation Normalizes Platelet Aggregation in Hypercholesterolemic Humans  

Microsoft Academic Search

Objectives. The present study was designed to test the hypothesis that long-term dietary supplementation with the nitric oxide precursor l-arginine would enhance vascular or platelet-derived nitric oxide activity, or both, and thereby inhibit platelet reactivity in hypercholesterolemic humans.Background. We have shown that reduced vascular activity of nitric oxide in hypercholesterolemic rabbits can be restored by l-arginine supplementation. The improvement in

Andreas Wolf; Christoff Zalpour; Gregor Theilmeier; Bing-yin Wang; Adrian Ma; Barbara Anderson; Philip S Tsao; John P Cooke




EPA Science Inventory

The objective of this investigation was to characterize 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...


Antihypertensive Effect of Long-Term Oral Administration of Jellyfish (Rhopilema esculentum) Collagen Peptides on Renovascular Hypertension  

PubMed Central

Antihypertensive effect of long-term oral administration of jellyfish (Rhopilema esculentum) collagen peptides (JCP) on renovascular hypertension rats (RVHs) was evaluated. The systolic blood pressure and diastolic blood pressure of the RVHs were significantly reduced with administration of JCP (p < 0.05), compared with model control group. However, the arterial blood pressure of normal rats showed no significant changes during long-term oral treatment with high dose JCP (p > 0.05). Furthermore, effect of JCP on angiotensin II (Ang II) concentration of plasma had no significance (p > 0.05), but JCP significantly inhibited the Ang II concentration in RVHs’ kidney (p < 0.05). The kidney should be the target site of JCP.

Zhuang, Yongliang; Sun, Liping; Zhang, Yufeng; Liu, Gaoxiang



Vibrational spectra of L-arginine nitrates  

NASA Astrophysics Data System (ADS)

Crystals L-arginine·'HNO 3·0.5H 2O and L-arginine·2HNO 3 have been studied by attenuated total reflection Fourier transform infrared (FTIR ATR) and Fourier transform Raman spectroscopy with taking into account their crystal structures.

Petrosyan, A. M.; Sukiasyan, R. P.



Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein-Barr virus  

PubMed Central

BACKGROUND The objectives of this study were to determine i) the prevalence of oral Epstein-Barr virus (EBV) in HIV-infected subjects compared to non-HIV controls, and ii) the effects of long-term use of antiretroviral therapy (ART) on the prevalence of oral EBV. METHODS A cross-sectional study was performed in HIV-infected subjects with and without ART, and non-HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS Forty-nine HIV-infected subjects; 37 on ART (age range 23–54 yr, mean 37 yr), 12 not on ART (age range 20–40 yr, mean 31 yr), and 20 non-HIV controls (age range 19–53 yr, mean 31 yr) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV-infected subjects than non-HIV controls (80% vs 20%, mean=12,118 vs. 134 copies/105 cells, p<0.001). HIV-infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean= 4,102 vs. 138,613 copies/105 cells, p=0.011). The numbers were significantly lower in those who received long-term ART compared with short-term (mean= 1,401 vs. 11,124 copies/105 cells, p=0.034). No significant difference was observed between the groups when using EBNA1 primers. CONCLUSIONS Prevalence of oral EBV was significantly higher in HIV-infected subjects than non-HIV-controls. The numbers of the virus was significantly decreased by ART. Long-term use of ART did not increase oral EBV.

Amornthatree, Korntip; Sriplung, Hutcha; Mitarnun, Winyou; Nittayananta, Wipawee



Oral health coordinators in long-term care--a pilot study.  


This pilot project tested a curricular and systems approach to improving the oral health care of nursing home residents in three facilities in New Hampshire. An oral health coordinator (OHC) was appointed in each facility to act as a liaison between nursing and dental staff, provide resources for nursing assistants, and ensure staff delivery of residents' daily oral care. During the study, residents' oral health status was assessed at four intervals and ongoing training was provided to nursing staff. At the conclusion of the pilot study, an evaluation of the results indicated an improvement in oral hygiene in all facilities. The role of the OHC showed promise when that person was active in holding nursing staff accountable for daily oral care of the residents. PMID:20415802

Pronych, Gilda J; Brown, Elizabeth J; Horsch, Karen; Mercer, Karen



Long-Term Effects of Oral L-Carnitine Supplementation on Anemia in Chronic Hemodialysis  

PubMed Central

Background The therapeutic role of L-carnitine (LC) on the anemia of chronic hemodialized patients is still controversial. In order to clarify the long-term effects of LC administration on renal anemia, an open, observational 12-month study was performed. Methods Twenty stable outpatients undergoing hemodialysis were administered LC 900 mg p.o. daily for 12 months. The recombinant human erythropoietin (rHuEPO) dose was adjusted monthly when necessary to maintain the target hemoglobin (Hb) levels. Results The free LC level increased, while the acyl/free LC ratio decreased significantly 3 months after administration and was then maintained until the end of the study. There was no difference in Hb levels and the erythropoietin resistance index (ERI) during the study period. However, it was observed that ERI decreased significantly in 7 out of 18 patients (responders) 5 months after LC administration and was maintained thereafter (almost 40% reduction of the rHuEPO dose). The acyl/free carnitine ratio at baseline was the most contributing factor distinguishing responders from nonresponders. Conclusion Although the beneficial effect of LC supplementation on renal anemia was not observed in all patients, at least 40% of the patients (responders) showed a significant improvement in ERI after long-term LC administration.

Kudoh, Yasuo; Aoyama, Shinya; Torii, Takaaki; Chen, Qijie; Nagahara, Daigo; Sakata, Hiromi; Nozawa, Akihiko



L-Arginine and Nitric Oxide in CNS Function and Neurodegenerative Diseases  

Microsoft Academic Search

One of the main functions of L-arginine (ARG) is the synthesis of nitric oxide (NO). NO is an important regulator of physiological processes in the central nervous system (CNS). NO promotes optimal cerebral blood flow, consolidates memory processes, facilitates long term potentiation, maintains sleep-wake cycles, and assists in normal olfaction. However, at pathological levels, NO adversely affects brain function producing

Mayur Virarkar; Lini Alappat; Peter G. Bradford; Atif B. Awad



The toxic effects of long-term, oral administration of L-tryptophan in rats with portacaval shunt.  

PubMed Central

The oral, long-term administration of 200 mg/kg of L-tryptophan to rats previously submitted to a portacaval shunt causes significant loss of body weight, muscular hypertonicity and aggressivity, as well as marked alterations of the liver structure. Conversely, the same treatment is well tolerated by control animals. It is postulated that the derangement of tryptophan metabolism normally occurring in rats with portacaval shunt is by itself insufficient to induce behavioural changes and liver damage, which, on the contrary, develop when tryptophan metabolism is further altered by the administration of the amino acid to the animals for a long period of time. Images Fig. 2 Fig. 3 Fig. 4

Bucci, L.; Chiavarelli, R.



L-arginine independent macrophage tumor cytotoxicity  

SciTech Connect

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.

Klostergaard, J.; Leroux, M.E. (Univ. of Texas, M. D. Anderson Cancer Center, Houston (USA))



Expression of oral secretory leukocyte protease inhibitor in HIV-infected subjects with long-term use of antiretroviral therapy  

PubMed Central

BACKGROUND The objectives of this study were to determine 1) expression of oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects compared to non-HIV controls, 2) the oral SLPI expression in HIV-infected subjects with ART compared to those without ART, and 3) factors associated with the expression of oral SLPI. METHODS Oral tissues and samples of both un-stimulated and stimulated saliva were collected from HIV-infected subjects with and without ART, and non-HIV individuals. The expression of SLPI mRNA in the tissue was determined by quantitative real-time PCR. Salivary SLPI protein was detected using ELISA. Chi-square test and logistic regression analysis were performed to determine the association between HIV/ART status and the expression of oral SLPI. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled; 99 on ART (age range 23–57 yr, mean 39 yr), 58 not on ART (age range 20–59 yr, mean 34 yr), and 50 non-HIV controls (age range 19–59 yr, mean 36 yr). The most common ART regimen was 2 NRTIs+1 NNRTI. The expression of oral SLPI in stimulated saliva was significantly decreased with HIV infection (p< 0.001). The expression was also significantly different with respect to ART use (p=0.007). Smoking, CD4+ cell count, and HIV viral load were the factors associated with the oral SLPI expression. CONCLUSION The expression of oral SLPI is altered by HIV infection and use of ART. Thus, oral SLPI may be the useful biomarker to identify subjects at risk of infections and malignant transformation due to HIV infection and long-term ART.

Nittayananta, Wipawee; Kemapunmanus, Marisa; Yangngam, Supaporn; Talungchit, Sineepat; Sriplung, Hutcha



Modulation of the L-arginine/nitric oxide signalling pathway in vascular endothelial cells.  


Nitric oxide (NO) is synthesized from L-arginine, and in endothelial cells influx of L-arginine is mediated predominantly via Na+-independent cationic amino acid transporters. Constitutive, Ca2+-calmodulin-sensitive eNOS (endothelial nitric oxide synthase) metabolizes L-arginine to NO and L-citrulline. eNOS is present in membrane caveolae and the cytosol and requires tetrahydrobiopterin, NADPH, FAD and FMN as additional cofactors for its activity. Supply of L-arginine for NO synthesis appears to be derived from a membrane-associated compartment distinct from the bulk intracellular amino acid pool, e.g. near invaginations of the plasma membrane referred to as 'lipid rafts' or caveolae. Co-localization of eNOS and the cationic amino acid transport system y+ in caveolae in part explains the 'arginine paradox', related to the phenomenon that in certain disease states eNOS requires an extracellular supply of L-arginine despite having sufficient intracellular L-arginine concentrations. Vasoactive agonists normally elevate [Ca2+]i (intracellular calcium concentration) in endothelial cells, thus stimulating NO production, whereas fluid shear stress, 17beta-oestradiol and insulin cause phosphorylation of the serine/threonine protein kinase Akt/protein kinase B in a phosphoinositide 3-kinase-dependent manner and activation of eNOS at basal [Ca2+]i levels. Adenosine causes an acute activation of p42/p44 mitogen-activated protein kinase and NO release, with membrane hyperpolarization leading to increased system y+ activity in fetal endothelial cells. In addition to acute stimulatory actions of D-glucose and insulin on L-arginine transport and NO synthesis, gestational diabetes, intrauterine growth retardation and pre-eclampsia induce phenotypic changes in the fetal vasculature, resulting in alterations in the L-arginine/NO signalling pathway and regulation of [Ca2+]i. These alterations may have significant implications for long-term programming of the fetal cardiovascular system. PMID:15777019

Wyatt, Amanda W; Steinert, Joern R; Mann, Giovanni E



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

ERIC Educational Resources Information Center

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)

Houle, Bonnie A.



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

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-Snail blocked xenograft tumorigenesis of long-term nicotine-treated OSCC cells.

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



Long-term oral sensitivity and feeding skills of low-risk pre-term infants  

Microsoft Academic Search

This study examined the oral sensitivity and feeding skills of low-risk pre-term infants at 11–17 months corrected age. Twenty pre-term infants (PT) born between 32 and 37 weeks at birth without any medical comorbidities were assessed. All of this PT group received supplemental nasogastric (NG) tube feeds during their birth-stay in hospital. A matched control group of 10 healthy full-term

Pamela Dodrill; Sandra McMahon; Elizabeth Ward; Kelly Weir; Tim Donovan; Bena Riddle



Long term treatment of pulmonary arterial hypertension with beraprost, an oral prostacyclin analogue  

Microsoft Academic Search

OBJECTIVETo evaluate the effects of one year's treatment with beraprost, an orally active prostacyclin analogue, in patients with severe pulmonary hypertension.PATIENTS13 patients with severe pulmonary hypertension. This was primary in nine, thromboembolic in three, and caused by Eisenmenger syndrome in one.METHODSAll patients underwent right heart catheterisation. Mean (SD) right atrial pressure was 5 (3) mm Hg, mean pulmonary artery pressure

C D Vizza; S Sciomer; S Morelli; C Lavalle; P Di Marzio; D Padovani; R Badagliacca; A R Vestri; R Naeije; F Fedele



Long-Term Surgical Complications in the Oral Cancer Patient: a Comprehensive Review. Part II  

PubMed Central

ABSTRACT Objectives Surgery remains the preferred treatment for the majority of oral cancers. The aim of the present article was to provide a comprehensive review of complications associated with surgical treatment of oral cancer including hardware failure; complications associated with choice of reconstruction, donor site morbidity as well as functional and aesthetic issues that impact on the quality of life. Material and Methods The available English language literature relevant to complications associated with surgical treatment of oral cancer was reviewed. Complications associated with potential for disfigurement, choice of reconstruction, donor site morbidity as well as functional and aesthetic issues that impact on the quality of life are summarized. Results In total 35 literature sources were obtained and reviewed. The topics covered in the second part of this review series include hardware failure, scars and fistula formation; complications associated with choice of reconstruction, donor site morbidity as well as functional and aesthetic issues. Conclusions Cancer resection should be planned around two very important concepts. First and foremost is the eradication of disease. This should be the ultimate goal of the ablative team and all potential complications that may be the result of appropriately executed oncologic resection should be discussed in details with the patient. Adequate reconstruction of the defects with restoration of form and function is the second, but not of less importance, goal for the successful care of the head and neck cancer patient.



A novel approach for long-term oral drug administration in animal research  

PubMed Central

In the field of pharmacological research, the oral consumption of anastrozole, an aromatase inhibitor, when added to an animal’s drinking water is hindered by poor drug palatability and environmental loss of drug solution. To overcome these caveats, we developed a novel approach for the oral delivery of anastrozole mixed in a solid hydration gel matrix that functions as a replacement for water. Heated hydration gel was mixed with anastrozole and distributed into a gel delivery device consisting of a 50 mL plastic conical tube containing four stacked 200 µL pipette tips to allow for air pressure induced gel disbursement. Transgenic female 3xTgAD mice were randomized to receive either anastrozole-treated or untreated hydration gel at 3 months of age. Body weights were recorded weekly, and gel consumption was measured every 1–3 days. Six months post treatment mice were killed and serum anastrozole levels were determined using liquid chromatography-mass spectrometry (LC-MS). Anastrozole-treated mice gained significantly more weight despite consuming significantly less hydration gel compared to vehicle treated mice. LC-MS analysis, using a low serum volume (10 µL), revealed average anastrozole serum levels of 2.91 ng/mL. Anastrozole-treated ovarian tissue displayed ovarian cysts, massive edema-like stroma, and also lacked corpa lutea compared to control mice. These findings demonstrate that hydration gel delivered using the newly developed oral delivery method is a viable approach for pharmacological research involving compounds with poor palatability, low water solubility, and cost prohibitive compounds where environmental loss needs to be minimized.

Overk, Cassia R.; Borgia, Jeffrey A.; Mufson, Elliott J.



Oral human ?-defensin 2 in HIV-infected subjects with long-term use of antiretroviral therapy  

PubMed Central

BACKGROUND The objectives of this study were to determine 1) oral hBD2 expression in HIV-infected subjects compared to non-HIV controls, 2) the expression of oral hBD2 in HIV-infected subjects with ART compared with those without ART, and 3) factors associated with the expression of oral hBD2. METHODS Oral examination and punched biopsy on buccal mucosa were performed in HIV-infected subjects with and without ART, and non-HIV individuals. The expression of hBD2 mRNA was determined by quantitative real-time PCR. Saliva samples of both un-stimulated and stimulated saliva were collected and analyzed for hBD2 levels using ELISA. Student’s t-test and nonparametric multi-way ANOVA test were used for comparison of measurements between or among groups. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled; 99 on ART (age range 23–57 yr, mean 39 yr), 58 not on ART (age range 20–59 yr, mean 34 yr), and 50 non-HIV controls (age range 19–59 yr, mean 36 yr). The most common ART regimen was 2 NRTIs+1 NNRTI. Salivary levels of hBD2 were significantly increased in HIV infection (p< 0.001). The levels of hBD2 in stimulated saliva were also found to be significantly different between HIV-infected subjects who were and were not on ART (p< 0.001). No significant difference was observed with the expression of hBD2 mRNA. CONCLUSION Oral innate immunity is affected by HIV infection and use of ART. Salivary hBD2 levels may be the useful biomarkers to monitor those on long-term ART who are at risk of developing oral infections and malignant transformation.

Nittayananta, Wipawee; Kemapunmanus, Marisa; Amornthatree, Kornthip; Talungchit, Sineepat; Sriplung, Hutcha



Orally active and long-term acting insulin-mimetic vanadyl complex:bis(picolinato)oxovanadium (IV).  


The blood glucose level of rats with streptozotocin (STZ)-induced diabetes has been found to be normalized by administration of vanadyl or vanadate complexes. During our investigations on the development of anti-diabetic vanadyl complexes with various types of coordination mode such as V-O, V-N and V-S, we found that a new bis(picolinato)oxovanadium (IV) complex (VPA) has a strong insulin-mimetic effects as evaluated by an in vitro experiments, in which the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine was observed to be similar to that of insulin. VPA was also effective for normalizing the blood glucose level of STZ-induced diabetic rats when given intraperitoneally or orally. The serum glucose level was maintained in the normal range for about 30 days with body weight gain after the end of oral administration of VPA for 14 days. VPA was confirmed to be an orally active and long-term acting insulin-mimetic vanadyl complex to treat insulin-dependent diabetes mellitus (IDDM) in rats. PMID:7575515

Sakurai, H; Fujii, K; Watanabe, H; Tamura, H



Antithrombotic effect of L-arginine in hypertensive rats.  


The aim of the study was to evaluate the effect of L-arginine (L-Arg) on haemostasis in stasis model of venous thrombosis in renal hypertensive rats. The effect of the single dose (i.v. 300 mg/kg bolus+300 mg/kg/h) and of the 10-day application (p.o. 1 g/kg, once daily) of L-Arg was determined. L-Arg reduced the blood pressure both in the acute and long-term application. The single dose of L-Arg decreased the occurrence rate of the thrombus whereas long-term administration reduced significantly the thrombus weight. There were no differences in prothrombin time and activated partial thromboplastin time while the fibrinogen concentration decreased both in the acute and the long-term experiment. L-Arg shortened euglobulin clot lysis time and bleeding time in the long-term application. The chronic L-Arg treatment also inhibited significantly collagen-induced platelet aggregation. The overall haemostasis and coagulation potentials were inhibited and the fibrinolysis potential was higher in the group receiving this amino-acid. The results show that L-Arg, in a complex way, evokes the antithrombotic effect in the model of venous thrombosis in hypertensive rats. PMID:15381827

Cylwik, D; Mogielnicki, A; Kramkowski, K; Stokowski, J; Buczko, W



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

PubMed Central

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.

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



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


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 T helper type 1 (Th1) and Th17 responses, and considerable evidence implicates interleukin (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 CD3+CD4-CD8- 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

Hernández-Santos, N; Huppler, A R; Peterson, A C; Khader, S A; McKenna, K C; Gaffen, S L



Differential long-term outcomes for voluntary and involuntary transition from injection to oral opioid maintenance treatment  

PubMed Central

Background The most widely used maintenance treatment for opioid dependency is substitution with long-acting oral opioids. Treatment with injectable diacetylmorphine provides an opportunity for patients to stabilize and possibly transition to oral treatment, if clinically indicated. The aim of this study was to explore outcomes of individuals that received injectable diacetylmorphine and voluntarily transitioned to oral methadone. Design and methods The North American Opiate Medication Initiative was a randomized controlled trial that compared the effectiveness of injectable diacetylmorphine (or hydromorphone) to oral methadone for long-term opioid-dependency. Treatment was provided for 12-months with an additional 3 months for transition and weaning. Participants were followed until 24-months from randomization. Among the participants randomized to injectable treatments, a sub-group voluntarily chose to transition to oral methadone (n?=?16) during the treatment period. Illicit heroin use and treatment retention were assessed at 24-months for those voluntarily and involuntarily transitioning (n?=?95) to oral methadone. Results At 24-months, the group that voluntarily transitioned to oral methadone had higher odds of treatment retention (adjusted odds ratio?=?5.55; 95% confidence interval [CI]?=?1.11, 27.81; Chi-square?=?4.33, df?=?1, p-value?=?0.037) than the involuntary transition group. At 24-months, the adjusted mean difference in prior 30 days of illicit heroin use for the voluntary, compared to the involuntary group was -5.58 (95% CI?=?-11.62, 0.47; t-value?=?-1.83, df?=?97.4, p-value?=?0.070). Conclusions Although the results of this study were based on small groups of self-selected (i.e., non-randomized) participants, our data underlines the critical importance of voluntary and patient-centered decision making. If we had continued offering treatment with diacetylmorphine, those retained to injectable medication may have sustained the achieved improvements in the first 12 months. Diversified opioid treatment should be available so patients and physicians can flexibly choose the best treatment at the time. Trial registration Clinical Trial Registration: NCT00175357



Molecular analysis of the microbiota in hard feces from healthy rabbits (Oryctolagus cuniculus) medicated with long term oral meloxicam  

PubMed Central

Background Analgesia is often indicated in rabbits undergoing surgical procedures or suffering from various painful conditions and the most common adverse effects associated with NSAIDs occur in the gastrointestinal tract (GIT). The objective of this study was to determine the potential effect of long-term (21 days) meloxicam administration on the fecal bacterial microbiota in healthy rabbits. Samples of hard feces were collected from six rabbits treated with meloxicam (1 mg/kg orally once every 24 h) on days 0,6,14 and 21. Next generation sequencing of V4 16S rRNA gene products was performed. Results A total of 2589912 V4 rRNA gene sequences passed all quality control filters. Firmicutes predominated (82.0?±?6.2%). Sixteen other phyla were also identified but other than Verrucomicrobia (4.4?±?4.9%), all accounted for less than 1% of the identified sequences. Within Firmicutes, Clostridia was the dominant class, accounting for 76% of operational taxon units (OTUs). In general, there were only few differences observed between time points and different rabbits at the phylum level. A significant change was observed in the relative abundance of Proteobacteria over the 4 time points (P?=?0.02). Conclusions The gastrointestinal tract of rabbits harbors dense and diverse microbiota. Significant alteration of the hard fecal microbiota does not appear to be a considerable adverse effect expected in rabbits treated for 21 days with oral meloxicam at a dose of 1 mg/kg.



Factors Associated with Long-Term Oral Hypoglycemic Agent Responsiveness in Korean Patients with Type 2 Diabetes Mellitus  

PubMed Central

Background This study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) responsiveness in Korean type 2 diabetic patients. Methods Two groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ?7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study. Results The OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, postprandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher proportion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes. Conclusion Lower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

Kim, Bo-Yeon; Jung, Chan-Hee; Mok, Ji-Oh



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

PubMed Central

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 routine basis and that patients are in the therapeutic range only 64% of the time. Overview of POC INR Devices POC INR devices offer an alternative to laboratory-based testing and venipuncture, enabling INR determination from a fingerstick sample of whole blood. Independent evaluations have shown POC devices to have an acceptable level of precision. They permit INR results to be determined immediately, allowing for more rapid medication adjustments. POC devices can be used in a variety of settings including physician offices, ACCs, long-term care facilities, pharmacies, or by the patients themselves through self-testing (PST) or self-management (PSM) techniques. With PST, patients measure their INR values and then contact their physician for instructions on dose adjustment, whereas with PSM, patients adjust the medication themselves based on pre-set algorithms. These models are not suitable for all patients and require the identification and education of suitable candidates. Potential advantages of POC devices include improved convenience to patients, better treatment compliance and satisfaction, more frequent monitoring and fewer thromboembolic and hemorrhagic complications. Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values, low thromboplastin sensitivity, inability to calculate a mean normal PT, and errors in INR determination in patients with antiphospholipid antibodies with certain instruments. Although treatment satisfaction and quality of life (QoL) may improve with POC INR monitoring, some patients may experience increased anxiety or preoccupation with their disease with these strategies. Evidence-Based Analysis Methods Research Questions 1. Effectiveness Does POC INR monitoring improve clinical outcomes in various settings compared to standard laboratory-based testing? Does POC INR monitoring impact patient satisfaction, QoL, compliance, acceptability, convenience compared to standard laboratory-based INR determination? Settings include primary care settings with use of POC INR dev



Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production  

Microsoft Academic Search

L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to enhance endothelial function and to reduce intimal plaque area in cholesterol (Chol)-fed rabbits. We have studied endogenous NO production in such animals in vitro (endothelium-dependent relaxations) and in vivo (assessed by urinary NO3? excretion) before and during chronic oral adminstration of L-arginine and an inhibitor of NO synthesis,

Rainer H. Böger; Stefanie M. Bode-Böger; Andreas Mügge; Sven Kienke; Ralph Brandes; Alexander Dwenger; Jürgen C. Frölich



Attenuation of mitochondrial injury by L-arginine preconditioning of the liver.  


The present study was aimed to evaluate the efficacy of L-arginine on mitochondrial function in ischemic and reperfusion (I/R) induced hepatic injury. Adult Wistar rat were subjected to 1 h of partial liver ischemia followed by 3 hour reperfusion. Eighteen wistar rats were divided into three groups viz. sham-operated control group (I) (n=6), ischemia and reperfusion (I/R) group (II) (n=6), L-arginine treated group (100 mg/kg body weight/daily by oral route for 7 days before induced ischemia reperfusion maneuver) (III) (n=6). Mitochondrial injury was assessed in terms of decreased (P<0.05) activities of mitochondrial antioxidant enzymes (GSH, SOD, CAT), respiratory marker enzymes (NADH dehydrogenase, cytochrome c oxidases) and hepatocytes nitric oxide production. Pre-treatment with L-arginine (10 mg/kg/p.o. for 7 days) significantly counteracted the alternations of hepatic enzymes and mitochondrial respiratory and antioxidant enzymes. In addition, electron microscopy and histopathology study showed the restoration of cellular normalcy and accredits the cytoprotective role of L-arginine against I/R induced hepatocellular injury. On the basis of these findings it may be concluded that L-arginine protects mitochondrial function in hepatic ischemic and reperfused liver. PMID:18806313

Chattopadhyay, Pronobesh; Shukla, Gunjan; Verma, Anurag; Wahi, A K



?-Carotene concentration in buccal mucosal cells with and without dysplastic oral leukoplakia after long-term ?-carotene supplementation in male smokers  

Microsoft Academic Search

Objective: To measure the ?-carotene concentration in buccal mucosal cells in smoking men who had received long-term ?-carotene (BC) supplementation in a controlled trial. To assess the association of cellular BC on the prevalence of dysplasia in oral leukoplakia.Design:An end-of-trial examination of a part of subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study.Subjects and methods:343 men who for 5–7

KE Liede; G Alfthan; JHP Hietanen; JK Haukka; LM Saxen; OP Heinonen



Long-term efficacy and safety of oral Viagra® (sildenafil citrate) in men with erectile dysfunction and the effect of randomised treatment withdrawal  

Microsoft Academic Search

The long-term efficacy and safety of oral Viagra® (sildenafil citrate), a selective phosphodiesterase 5 inhibitor, and the effect of withdrawing treatment were evaluated in men with erectile dysfunction (ED). In 233 men with ED of psychogenic or mixed organic\\/psychogenic aetiology, 16 weeks of open-label, flexible-dose sildenafil treatment (10–100 mg) was followed by eight weeks of double-blind, fixed-dose, randomised withdrawal to

E Christiansen; WR Guirguis; D Cox; IH Osterloh



Elevated l-Arginine\\/Dimethylarginine Ratio Contributes to Enhanced Systemic NO Production by Dietary l-Arginine in Hypercholesterolemic Rabbits  

Microsoft Academic Search

Dietary supplementation of L-arginine, the precursor of endogenous NO, has been shown to enhance endothelial function in the cholesterol-fed rabbits. However, the mechanism by which dietary L-arginine accomplishes these effects has been unclear. In the present study we have assessed the plasma concentrations of L-arginine and of asymmetrical dimethylarginine (ADMA), a known endogenous inhibitor of NO synthase, in cholesterol-fed rabbits

Stefanie M. Bode-Böger; Rainer H. Böger; Sven Kienke; Wolfgang Junker; Jürgen C. Frölich



L-Arginine and Alzheimer's Disease  

PubMed Central

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.

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



Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats.  


Osteoarthritis is a chronic, painful condition that is now recognised as affecting a large proportion of cats. Non-steroidal anti-inflammatory drugs (NSAIDs) have proven efficacy in dogs and humans but there are limited published data on the use of NSAIDs in the long-term management of this condition in cats. This prospective study aimed to assess the long-term safety and palatability of oral meloxicam and its efficacy in treating osteoarthritic pain in cats when given at a dose of 0.01-0.03 mg/kg once daily. Forty cats diagnosed with osteoarthritis completed the trial with a mean treatment duration of 5.8 months. Gastrointestinal upset in 2/46 (4%) cats was the only adverse effect noted. No deleterious effect on renal function was detected in cats studied. Owners subjectively assessed treatment efficacy as good or excellent in 34/40 (85%) of cases. The results of this study showed oral meloxicam to be safe and palatable long-term treatment for osteoarthritis in cats when given with food at a dose of 0.01-0.03 mg/kg. PMID:18440263

Gunew, Marcus N; Menrath, Victor H; Marshall, Rhett D



Regulation of immune responses by L-arginine metabolism  

Microsoft Academic Search

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

Paola Zanovello; Vincenzo Bronte



Long-Term Outcomes of a Dental Postbaccalaureate Program: Increasing Dental Student Diversity and Oral Health Care Access  

PubMed Central

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.

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



L-arginine and nitric oxide in CNS function and neurodegenerative diseases.  


One of the main functions of L-arginine (ARG) is the synthesis of nitric oxide (NO). NO is an important regulator of physiological processes in the central nervous system (CNS). NO promotes optimal cerebral blood flow, consolidates memory processes, facilitates long-term potentiation, maintains sleep-wake cycles, and assists in normal olfaction. However, at pathological levels, NO adversely affects brain function producing nitroxidative stress and promoting development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and other disorders of the CNS. This review summarizes current knowledge of the role of NO in the CNS and the role of diet in regulating the levels of NO. PMID:24007420

Virarkar, Mayur; Alappat, Lini; Bradford, Peter G; Awad, Atif B



The effect of long-term oral dantrolene on the neuromuscular action of rocuronium: a case report.  


Oral dantrolene causes a dose-dependent depression of skeletal muscle contractility. A 52-year-old man treated with oral dantrolene for spasticity after spinal cord injury was scheduled to undergo irrigation and drainage of a thigh abscess under general anesthesia. He had taken 50 mg oral dantrolene per day for 3 years. Under standard neuromuscular monitoring, anesthesia was performed with propofol, rocuronium, and sevoflurane. A bolus dose of ED95 (0.3 mg/kg) of rocuronium could not depress T1 up to 95%. An additional dose of rocuronium depressed T1 completely and decreased the train-of-four (TOF) count to zero. There was no apparent prolongation of the neuromuscular blocking action of rocuronium. The TOF ratio was recovered to more than 0.9 within 40 minutes after the last dose of rocuronium. A small dose of oral dantrolene does not prolong the duration of action and recovery of rocuronium. PMID:24624274

Jeon, Jinwoo; Song, Sejin; Kim, Mun-Cheol; Kim, Kye-Min; Lee, Sangseok



The effect of long-term oral dantrolene on the neuromuscular action of rocuronium: a case report  

PubMed Central

Oral dantrolene causes a dose-dependent depression of skeletal muscle contractility. A 52-year-old man treated with oral dantrolene for spasticity after spinal cord injury was scheduled to undergo irrigation and drainage of a thigh abscess under general anesthesia. He had taken 50 mg oral dantrolene per day for 3 years. Under standard neuromuscular monitoring, anesthesia was performed with propofol, rocuronium, and sevoflurane. A bolus dose of ED95 (0.3 mg/kg) of rocuronium could not depress T1 up to 95%. An additional dose of rocuronium depressed T1 completely and decreased the train-of-four (TOF) count to zero. There was no apparent prolongation of the neuromuscular blocking action of rocuronium. The TOF ratio was recovered to more than 0.9 within 40 minutes after the last dose of rocuronium. A small dose of oral dantrolene does not prolong the duration of action and recovery of rocuronium.

Jeon, Jinwoo; Song, Sejin; Kim, Mun-Cheol; Kim, Kye-Min



The Effects of Caffeine on l Arginine Metabolism in the Brain of Rats  

Microsoft Academic Search

In our study, the short-term effects of caffeine on L- arginine metabolism in the brains of rats were investigated. Caffeine\\u000a was given orally at two different doses: 30 mg\\/kg and 100 mg\\/kg (a high non-toxic dose). Brain tissue arginase activity in\\u000a rats from the caffeine-treated groups decreased significantly compared with the control group. Malondialdehyde (MDA) levels\\u000a in the brain tissue

Ebru Ofluoglu; Hatice Pasaoglu; Ayd?n Pasaoglu



Effect of pravastatin on responsiveness to N-monomethyl- l-arginine in patients with hypercholesterolaemia  

Microsoft Academic Search

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

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



Long-term results of oral valganciclovir for treatment of anterior segment inflammation secondary to cytomegalovirus infection  

PubMed Central

Background The purpose of this study was to assess the efficacy of oral valganciclovir in the treatment of anterior segment inflammation caused by cytomegalovirus (CMV) infection. Methods Consecutive patients with anterior segment inflammation due to CMV causing anterior uveitis or corneal endotheliitis treated with oral valganciclovir were reviewed. Diagnosis of CMV infection was confirmed by polymerase chain reaction of the aqueous aspirate prior to commencement of oral valganciclovir. All patients were treated with an oral loading dose of 900 mg valganciclovir twice daily for at least 2 weeks, followed by an additional 450 mg valganciclovir twice-daily maintenance therapy. Changes in visual acuity, intraocular pressure (IOP), use of antiglaucomatous eye drops, and recurrence were analyzed. Results Thirteen eyes of 11 patients were followed for a mean of 17.2 months. Two patients had bilateral corneal endotheliitis. All eyes had absence of anterior segment inflammation within 3 weeks after treatment. Following treatment, the mean logMAR visual acuity improved significantly from 0.58 at baseline to 0.37 at the last follow-up (P = 0.048). The mean IOP and number of antiglaucomatous eye drops also decreased significantly (P = 0.021 and P = 0.004, respectively). Five (38.5%) eyes had recurrence of anterior uveitis after valganciclovir was stopped and required retreatment with oral valganciclovir. Conclusion Oral valganciclovir appeared to be effective in controlling CMV anterior uveitis, resulting in visual improvement and IOP reduction following control of inflammation. However, despite the initial clinical response in all cases, recurrence after cessation of oral valganciclovir could occur.

Wong, Victoria WY; Chan, Carmen KM; Leung, Dexter YL; Lai, Timothy YY



Long-term administration of beraprost, an oral prostacyclin analogue, improves pulmonary diffusion capacity in patients with systemic sclerosis  

Microsoft Academic Search

The objective of this study was to assess the effect of beraprost sodium, an oral prostacyclin analogue, on pulmonary function in patients with systemic sclerosis. Seventeen patients, with systemic sclerosis and predicted percent values of carbon monoxide diffusion capacity (%DLCO) of less than 95, received beraprost sodium for at least 12 months. Conventional testing for pulmonary function was performed at

Y. Matsukawa; O. Saito; M. Aoki; M. Abe; S. Nishinarita; S. Sawada; T. Horie; S. Naruse; M. Hiranuma



Second-line chemotherapy with long-term low-dose oral etoposide in patients with advanced breast cancer  

Microsoft Academic Search

In a phase II study, 27 patients with metastatic breast cancer were treated with oral etoposide as second-line chemotherapy at a dose of 50 mg\\/m2\\/day for 21 days, which courses were repeated every 4 weeks. Twenty-one patients were evaluable for response, and twenty-five for toxicity. In two (10%) patients a partial response was observed with a duration of 60 and

M. Bontenbal; A. S. Th. Planting; J. Verweij; R. Wit; W. H. J. Kruit; G. Stoter; J. G. M. Klijn



Effects of long-term silymarin oral supplementation on the blood biochemical profile of rainbow trout (Oncorhynchus mykiss).  


Silymarin, an extract from "milk thistle" (Silybum marianum) plant is traditionally used as herbal medicine. The present study was conducted to investigate the clinical effects and possible side effects of silymarin on biochemical blood parameters of rainbow trout (Oncorhynchus mykiss). Fishes were treated with 0 (control), 100, 400, and 800 mg of silymarin per kg of food during 4 weeks. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine kinase (CK), glucose, total protein, creatinine, triglyceride, cholesterol, urea, uric acid and liver cellular total antioxidant, and protein content were measured after 7, 14, and 28 days of silymarin treatment. The results showed that oral administration of silymarin in fish significantly reduced plasma glucose and cholesterol levels and relatively increased plasma total protein and globulin concentrations (P < 0.05). Increasing plasma albumin levels indicate the important role of albumin in drug transportation in circulatory system of fish. Silymarin also stabilized cellular membrane structure and regulated the levels of AST, ALT, ALP, CK, and LDH activity. In conclusion, on the basis of these results, oral administration of silymarin up to 400 mg per 1 kg of food has no side effect on blood biochemical and clinical parameters of fishes. However, oral administration of 800 mg/kg- of silymarin caused cytotoxicity and modifications in blood biochemical parameters of fish. PMID:21519846

Banaee, Mahdi; Sureda, Antoni; Mirvaghefi, Ali Reza; Rafei, Golam Reza



Oxidative Stress and Asymmetric Dimethylarginine Are Associated with Cardiovascular Complications in Hemodialysis Patients: Improvements by L-Arginine Intake  

Microsoft Academic Search

Background\\/Aim: High incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) patients is a result of an interlaced relation between oxidative stress, endothelial dysfunction (ED) and inflammation. This study tries to investigate the development of these processes in CKD patients receiving conservative treatment or on hemodialysis (HD). We also examined the modulating effect of oral L-arginine in HD patients

Hala O. El-Mesallamy; Sherehan G. Abdel Hamid; Mohamed Z. Gad



[A case of Stage IV sigmoid colon cancer that achieved long-term survival with oral anticancer drugs].  


An 80-year-old man presenting with abdominal distension was admitted to our hospital. He was diagnosed with sigmoid cancer with multiple liver and lung metastases. We first performed a sigmoidectomy to avoid obstruction, and then initiated chemotherapy with S-1(120mg/day). The tumor showed a complete clinical response after 10 courses, but we had to change the regimen after 18 courses because of growth of the lung metastases. After 10 courses of capecitabine(4,200mg/ day)treatment, we again observed growth of the lung metastases; a new nodule, which was also considered to be a metastasis, appeared on the abdominal wall. We then decided to administer mFOLFOX6(5-fluorouracil+Leucovorin+oxaliplatin) after the patient had received oral anticancer drugs for 3 years 4 month. In conclusion, oral chemotherapy drugs may prevent tumor growth over a long period and improve quality of life(QOL)in elderly patients with Stage IV colon cancer. PMID:24743289

Hasegawa, Yako; Iwata, Hideyuki; Hatanaka, Masayuki



Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice.  


The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo. These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice. PMID:19854266

Rodriguez-Cuenca, Sergio; Cochemé, Helena M; Logan, Angela; Abakumova, Irina; Prime, Tracy A; Rose, Claudia; Vidal-Puig, Antonio; Smith, Anthony C; Rubinsztein, David C; Fearnley, Ian M; Jones, Bruce A; Pope, Simon; Heales, Simon J R; Lam, Brian Y H; Neogi, Sudeshna Guha; McFarlane, Ian; James, Andrew M; Smith, Robin A J; Murphy, Michael P



L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial  

PubMed Central

Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference ?3%, 95% CI ?19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI ?9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. Registry Registry number: NCT00677339

Ralph, Anna P.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B.; Yeo, Tsin W.; Chatfield, Mark D.; Soemanto, Retno K.; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P.; Eisman, John; Price, Ric N.; Morris, Peter S.; Kelly, Paul M.; Anstey, Nicholas M.



The long term oral regulation of blood glucose in diabetic patients by using of Escherichia coli Nissle 1917 expressing CTB-IGF-1 hybrid protein.  


Regarding to the high prevalence and comorbidities of chronic high blood glucose in diabetic patients and the limited efficacy and current painful treatments. It is necessary to improve new treatments that are non-invasive and long-term for controlling blood glucose. Recent studies have shown that the healthy microflora in different body organs can perform as the gene vectors for expressing different types of gene therapies in situ. We have proposed that by constructing a recombinant Escherichia coli Nissle 1917 that expresses CTB-IGF-1 hybrid gene under control of ompC glucose sensitive promoter, the intestinal glucose level can be regulated. This method in comparison with other methods is a non-invasive way to control the blood glucose orally and it can be used for all types of diabetes. PMID:24074833

Bazi, Zahra; Jalili, Mahsa; Hekmatdoost, Azita



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

PubMed Central

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.

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



Patient Self-Management of Oral Anticoagulation with Vitamin K Antagonists in Everyday Practice: Efficacy and Safety in a Nationwide Long-Term Prospective Cohort Study  

PubMed Central

Patient self-management (PSM) of oral anticoagulation is under discussion, because evidence from real-life settings is missing. Using data from a nationwide, prospective cohort study in Switzerland, we assessed overall long-term efficacy and safety of PSM and examined subgroups. Data of 1140 patients (5818.9 patient-years) were analysed and no patient were lost to follow-up. Median follow-up was 4.3 years (range 0.2–12.8 years). Median age at the time of training was 54.2 years (range 18.2–85.2) and 34.6% were women. All-cause mortality was 1.4 per 100 patient-years (95% CI 1.1–1.7) with a higher rate in patients with atrial fibrillation (2.5; 1.6–3.7; p<0.001), patients>50 years of age (2.0; 1.6–2.6; p<0.001), and men (1.6; 1.2–2.1; p?=?0.036). The rate of thromboembolic events was 0.4 (0.2–0.6) and independent from indications, sex and age. Major bleeding were observed in 1.1 (0.9–1.5) per 100 patient-years. Efficacy was comparable to standard care and new oral anticoagulants in a network meta-analysis. PSM of properly trained patients is effective and safe in a long-term real-life setting and robust across clinical subgroups. Adoption in various clinical settings, including those with limited access to medical care or rural areas is warranted.

Nagler, Michael; Bachmann, Lucas M.; Schmid, Pirmin; Raddatz Muller, Pascale; Wuillemin, Walter A.



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


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

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



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

SciTech Connect

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.

Stowe, H.D.; Thomas, J.W.; Johnson, T.; Marteniuk, J.V.; Morrow, D.A.; Ullrey, D.E. (Michigan State Univ., East Lansing (USA))



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

PubMed Central

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.

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



Long Term Care Study.  

National Technical Information Service (NTIS)

Long-term care needs and facilities in Saginaw, Mich., and alternatives to institutionalization were investigated. The instrument for the study was designed by the East Central Michigan Health Systems Agency. Long-term care facilities in Saginaw were surv...



Long-term degradation of resin-based cements in substances present in the oral environment: influence of activation mode  

PubMed Central

Indirect restorations in contact with free gingival margins or principally within the gingival sulcus, where the presence of organic acids produced by oral biofilm is higher, may present faster degradation of the resin-based cement pellicle. Objectives: To investigate the degradation of four resin-based cements: Rely X ARC (R), Variolink II (V), enforce (E) and All Cem (A), after immersion in distilled water (DW), lactic acid (LA) and artificial saliva (AS) and to analyze the influence of the activation mode on this response. Material and Methods: Two activation modes were evaluated: chemical (Ch) and dual (D). In the dual activation, a two-millimeter thick ceramic disk (IPS empress System) was interposed between the specimen and light-curing unit tip. Specimens were desiccated, immersed in distilled water, artificial saliva and lactic acid 0.1 M at 37ºC for 180 days, weighed daily for the first 7 days, and after 14, 21, 28, 90 and 180 days and were desiccated again. Sorption and solubility (µg/mm3) were calculated based on ISO 4049. The data were submitted to multifactor analysis of variance (MANOVA) and Tukey's HSD test for media comparisons (?=0.05). Results: Sorption was higher after immersion in LA (p<0.05) and increased significantly with time (p<0.05). Sorption was influenced by the activation mode: Ch>D (p<0.05). The lowest solubility was presented by R (p<0.05). Conclusions: Lactic acid increased the degradation of resin-based cements. Moreover, the physical component of activation, i.e., light-activation, contributed to a low degradation of resin-based cements.

da SILVA, Eduardo Moreira; NORONHA-FILHO, Jaime Dutra; AMARAL, Cristiane Mariote; POSKUS, Laiza Tatiana; GUIMARAES, Jose Guilherme Antunes



Pattern of resolution of pulmonary hypertension, long-term allograft right ventricular function, and exercise capacity in high-risk heart transplant recipients listed under oral sildenafil.  


Unresponsive pulmonary hypertension (PH) implies poor posttransplant outcomes. Data on late adaptation of the right ventricle (RV) are still few. This study evaluated three-yr RV function and remodeling, exercise capacity, and hemodynamic data in a selected group of patients initially disqualified because of PH. Between May 2005 and December 2009, 31 consecutive patients were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-wk trial, RHC disclosed PH reversibility (mean PVR: 5.41 ± 3 Wood units, mean TPG 14.5 ± 5.6 mmHg, and mean systolic PAP 68.9 ± 15.1 mmHg), allowing listing even though as high-risk procedures. All patients underwent heart transplantation. RV failure developed in three patients (9.6%), and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary hemodynamic profile normalization within the third postoperative month, allowing weaning from sildenafil in the 30 hospital survivors. One- and three-yr RHCs confirmed stable PH reversal (n = 26, all three-yr survivors). Parameters of late RV function and remodeling proved satisfactory. Parameters of functional capacity (Vo2 peak 19.7 ± 3.6 mL/kg/min and slope VE/Vco2 34.8 ± 2.7) proved homogeneous to those measured in transplant recipients with normal preoperative pulmonary artery pressure. Oral sildenafil is effective in allowing candidacy, safe transplantation, and long-term survival in PH recipients initially disqualified. PMID:24828060

De Santo, Luca S; Buonocore, Marianna; Agrusta, Federica; Bancone, Ciro; Galdieri, Nicola; Romano, Gianpaolo; Maiello, Ciro; Amarelli, Cristiano



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

PubMed Central

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 assessments, and other design issues limited generalizability and interpretation relative to the study hypothesis.

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



l-Arginine Supplementation and Metabolism in Asthma  

PubMed Central

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

Kenyon, Nicholas J.; Last, Michael; Bratt, Jennifer M.; Kwan, Vivian W.; O'Roark, Erin; Linderholm, Angela



Long-term quality of life and its predictive factors after oncologic surgery and microvascular reconstruction in patients with oral or oropharyngeal cancer.  


The aims of this study were to evaluate long-term quality of life (QoL) and to determine its predictive factors after oncologic surgery and free flap reconstruction in patients with oral or oropharyngeal cancer. Patients treated at our institution between 2000 and 2009, who are alive and disease-free at least 1 year after therapy, completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific H&N35 module. Eighty patients were included in our study. Global QoL score was 69.3 ± 22.7%. Global QoL and general symptoms were correlated with T stage, whereas head and neck symptoms were correlated with T stage and tumor involvement of the tongue base. Emotional and social functioning scales, and resumption of professional activity were significantly associated with global QoL. In conclusion, T stage, tumor involvement of the tongue base, professional status and emotional and social functions were the main determinants of QoL in our study. PMID:23771320

Pierre, Cédric S; Dassonville, Olivier; Chamorey, Emmanuel; Poissonnet, Gilles; Ettaiche, Marc; Santini, José; Peyrade, Frédéric; Benezery, Karen; Sudaka, Anne; Bozec, Alexandre



Long-term results of the phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed or refractory Waldenstrom Macroglobulinemia.  


Everolimus is an oral raptor mTOR inhibitor and has shown activity in patients with Waldenstrom's macroglobulinemia (WM). This study examines a large cohort of patients with relapsed/refractory WM with long-term follow up for survival. Patients were eligible if they had measurable disease, a platelet count >75,000 x 10(6)/L, an absolute neutrophil count >1,000 x 10(6)/L. Patients received everolimus 10 mg PO daily and were evaluated monthly. A success was defined as a complete or partial response (PR); minor responses (MR) were recorded and considered to be of clinical benefit. Sixty patients were enrolled and treated. The overall response rate (ORR) was 50% (all PR); the clinical benefit rate including MR or better was 73% (95% CI: 60-84%) with 23% MR. The median time to response for patients who achieved PR was 2 months (range, 1-26). The median duration of response has not been reached and median progression-free survival (PFS) was 21 months. Grade 3 or higher toxicities (at least possibly related to everolimus) were observed in 67% of patients. The most common grade 3 or 4 toxicities were anemia (27%), leukopenia (22%), and thrombocytopenia (20%). Other nonhematological toxicities were diarrhea (5%), fatigue (8%), stomatitis (8%) and pulmonary toxicity (5%). Everolimus has a high single-agent activity of 73% including MR, with a progression free survival of 21 months, indicating that this agent is active in relapsed/refractory WM. PMID:24716234

Ghobrial, Irene M; Witzig, Thomas E; Gertz, Morie; LaPlant, Betsy; Hayman, Suzanne; Camoriano, John; Lacy, Martha; Bergsagel, P Leif; Chuma, Stacey; DeAngelo, Daniel; Treon, Steven P



Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment of pelvic pain associated with endometriosis.  


The tolerability and effectiveness of depot medroxyprogesterone acetate (DMPA), compared with an oral contraceptive (OC) combined with low-dose danazol, in the long-term treatment of pelvic pain in women with endometriosis were evaluated in a randomized clinical trial. 40 women were allocated to each treatment regimen. At the 1-year assessment, a significant decrease was observed in all symptom scores of the visual analog and the verbal rating scale in both study groups. Only pain at menstruation was significantly greater in women in the OC group (because of the absence of regular flow in subjects in the DMPA group). In the DMPA group, 1 woman (2.5%) was very satisfied with her treatment, 28 (70%) were satisfied, 2 (5%) were uncertain, and 1 (2.5%) was very dissatisfied. Corresponding figures for the OC-danazol group were 6 (15%), 17 (42.5%), 4 (10%), 12 (30%), and 1 (2.5%). Overall, 72.5% of women in the DMPA group compared with 57.5% of those in the OC group were pleased after 1 year of treatment. It was concluded that, in selected women with highly symptomatic endometriosis, DMPA offers good analgesic results with tolerable side effects. PMID:8765259

Vercellini, P; De Giorgi, O; Oldani, S; Cortesi, I; Panazza, S; Crosignani, P G



Antiatherogenic effects of L-arginine in the hypercholesterolemic rabbit.  

PubMed Central

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.

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



The role of nitric oxide in the pathogenesis of spontaneous murine autoimmune disease: increased nitric oxide production and nitric oxide synthase expression in MRL-lpr/lpr mice, and reduction of spontaneous glomerulonephritis and arthritis by orally administered NG-monomethyl-L- arginine  

PubMed Central

MRL-lpr/lpr mice spontaneously develop various manifestations of autoimmunity including an inflammatory arthropathy and immune complex glomerulonephritis. This study examines the role of nitric oxide, a molecule with proinflammatory actions, in the pathogenesis of MRL- lpr/lpr autoimmune disease. MRL-lpr/lpr mice excreted more urinary nitrite/nitrate (an in vivo marker of nitric oxide production) than did mice of normal strains and MRL-(+/+) and B6-lpr/lpr congenic strains. In addition, MRL-lpr/lpr peritoneal macrophages had an enhanced capacity to produce nitric oxide in vitro as well as increased nitric oxide synthase activity, and certain tissues from MRL-lpr/lpr mice had increased expression of inducible nitric oxide synthase (NOS) mRNA and increased amounts of material immunoreactive for inducible NOS. Oral administration of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, prevented the development of glomerulonephritis and reduced the intensity of inflammatory arthritis in MRL-lpr/lpr mice. By using interspecific backcross mice, the gene for inducible NOS (Nosi) was mapped to mouse chromosome 11. This chromosomal localization was different from those loci that we have previously demonstrated to be linked to enhanced susceptibility to renal disease in an MRL-lpr/lpr cross. However, the chromosomal location of the NOS gene was consistent with an insulin-dependent diabetes locus identified in an analysis of nonobese diabetic (NOD) mice. These results suggest that elevated nitric oxide production could be important in the pathogenesis of autoimmunity, and that treatments to block the production of nitric oxide or block its effects might be valuable therapeutically.



Growth mechanism, dislocation etching and mechanical properties of L-arginine phosphate and deuterated L-arginine phosphate  

NASA Astrophysics Data System (ADS)

Single crystals of L-arginine phosphate monohydrate and its deuterated analog were grown from aqueous solutions. The effect of pH variation on the growth of microbes in these solutions was studied. Efforts were undertaken to minimize microbial incorporation into these crystals. The grown crystals were characterized by recording the powder diffraction and identifying the diffracting planes.

Venkataramanan, V.; Dhanaraj, G.; Bhat, H. L.



Long Term Ecological Resources  

NSDL National Science Digital Library

Students analyze data on temperature and precipitation collected from 26 different Long Term Ecological Research sites and compare them with annual net primary productivity. The students then form an ecological rule to explain their results.

Cooper, Scott


Insulin Secretion from Pancreatic B Cells Caused by L-Arginine-Derived Nitrogen Oxides  

Microsoft Academic Search

L-Arginine causes insulin release from pancreatic B cells. Data from three model systems support the hypothesis that L-arginine-derived nitrogen oxides (NOs) mediate insulin release stimulated by L-arginine in the presence of D-glucose and by the hypoglycemic drug tolbutamide. The formation of NO in pancreatic B cells was detected both chemically and by the NO-induced accumulation of guanosine 3',5'-monophosphate. N^G-substituted L-arginine

Harald H. H. W. Schmidt; Timothy D. Warner; Kunio Ishii; Hong Sheng; Ferid Murad



Long-term safety, efficacy and palatability of oral meloxicam at 0.01–0.03 mg\\/kg for treatment of osteoarthritic pain in cats  

Microsoft Academic Search

Osteoarthritis is a chronic, painful condition that is now recognised as affecting a large proportion of cats. Non-steroidal anti-inflammatory drugs (NSAIDs) have proven efficacy in dogs and humans but there are limited published data on the use of NSAIDs in the long-term management of this condition in cats. This prospective study aimed to assess the long-term safety and palatability of

Marcus N. Gunew; Victor H. Menrath; Rhett D. Marshall



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


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 neurons contribute to this basal nitric oxide release. PMID:1522509

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



A novel L-arginine salt nonlinear optical crystal: L-arginine p-nitrobenzoate monohydrate (LANB)  

NASA Astrophysics Data System (ADS)

A novel L-arginine salt nonlinear optical single crystal, L-arginine p-nitrobenzoate monohydrate (LANB) has been grown by slow cooling method from aqueous solution. Its solubility at different temperatures in water was measured. The grown crystal was characterized by the elemental analyses, X-ray single crystal and powder diffractions, Fourier transform infrared and Raman spectra. The structure analysis revealed that LANB belongs to the monoclinic crystallographic system, space group P21, with unit cell parameters: a = 8.566(3), b = 5.817(2), c = 17.131(7) Å, ? = 101.223(5)°, Z = 2 and V = 837.2(6) Å3. The proton and carbon configurations of L-arginine were confirmed through 1H NMR and 13C NMR spectra analyses. The linear and nonlinear optical properties of LANB crystal were studied by the use of transmission spectrum and second harmonic generation (SHG). The thermal properties were investigated by using thermo gravimetric (TG) and differential thermal analysis (DTA).

Wang, L.; Zhang, G. H.; Liu, X. T.; Wang, L. N.; Wang, X. Q.; Zhu, L. Y.; Xu, D.



Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages.  

PubMed Central

The microbiostatic action of macrophages was studied in vitro employing peritoneal cytotoxic macrophages (CM) from mice acting against Cryptococcus neoformans cultured in Dulbecco's medium with 10% dialyzed fetal bovine serum. Fungistasis was measured using electronic particle counting after lysis of macrophages with detergent. Macrophage fungistasis failed in medium lacking only L-arginine. Complete fungistasis was restored by L-arginine; restoration was concentration dependent, maximal at 200 microM. Deletion of all other essential amino acids did not abrogate fungistasis provided that L-arginine was present. Of twenty guanido compounds, including D-arginine, only three (L-arginine, L-homoarginine, and L-arginine methylester) supported fungistasis. Known activators or mediators of macrophage cytotoxicity (endotoxin, interferon gamma, tumor necrosis factor) did not replace L-arginine for CM-mediated fungistasis. The guanido analogue NG-monomethyl-L-arginine was a potent competitive inhibitor of CM-mediated fungistasis giving 50% inhibition at an inhibitor/L-arginine ratio of 1:27. Although CM completely blocked fungal reproduction via an L-arginine-dependent mechanism, the majority of the dormant fungi remained viable. Thus, this mechanism is viewed as a microbiostatic process similar or identical to the tumoristatic effect of macrophages. This suggests the production of a broad spectrum biostatic metabolite(s) upon consumption of L-arginine by cytotoxic macrophages.

Granger, D L; Hibbs, J B; Perfect, J R; Durack, D T



L-Arginine availability modulates local nitric oxide production and parasite killing in experimental trypanosomiasis.  


Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages from Trypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence of L-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows that L-arginine availability modulates NO production. Trypanosomes use L-arginine for polyamine synthesis, required for DNA and trypanothione synthesis. Moreover, arginase activity is up-regulated in macrophages from infected mice from the first days of infection. Arginase competes with NOS-II for their common substrate, L-arginine. In vitro, arginase inhibitors decreased urea production, increased macrophage nitrite production, and restored trypanosome killing. In vivo, a dramatic decrease in L-arginine concentration was observed in plasma from infected mice. In situ restoration of NO production and trypanosome killing were observed when excess L-arginine, but not D-arginine or L-arginine plus N(omega)-nitro-L-arginine (a NOS inhibitor), was injected into the peritoneum of infected mice. These data indicate the role of L-arginine depletion, induced by arginase and parasites, in modulating the L-arginine-NO pathway under pathophysiological conditions. PMID:10899869

Gobert, A P; Daulouede, S; Lepoivre, M; Boucher, J L; Bouteille, B; Buguet, A; Cespuglio, R; Veyret, B; Vincendeau, P



Measurement of L-arginine trifluoroacetate crystal nucleation kinetics  

NASA Astrophysics Data System (ADS)

The nucleation parameters such as critical radius, critical free energy change, and critical free energy barrier have been estimated for L-arginine trifluoroacetate single crystals on the basis of the classical homogeneous nucleation theory. Metastable zonewidth ranging in the extent of 7-10° was determined employing the polythermal method. The induction period measurements were also made and it was observed that the induction period decreases with increase in the supersaturation, and hence the nucleation is more probable for the higher value of supersaturation. Bulk crystals were grown successfully from the optimized growth nucleation parameters.

Liu, Xiaojing; Wang, Zeyan; Duan, Aidong; Zhang, Guanghui; Wang, Xinqiang; Sun, Zhihua; Zhu, Luyi; Yu, Gang; Sun, Guihua; Xu, Dong



Long-term treatment of venous thromboembolism.  


Long term treatment of venous thromboembolism is essential to complete therapy of the index episode and to reduce recurrences. Vitamin K antagonists are the mainstay for the long term treatment of venous thromboembolism for the majority of the patients as they allow oral administration. Low-molecular weight heparins are recommended for the long term treatment of cancer patients. The duration of long term anticoagulation depends on the features of the index venous thromboembolism and on the presence of associated risk factors. Patients at high risk for recurrence - mainly those who suffered unprovoked venous thromboembolism and those with cancer - should be evaluated for extended anticoagulation. The risk for major bleeding complications and the inconvenience for monitoring, dose adjustment and drug-food interactions are the main constraints for indefinite anticoagulant treatment. New anticoagulants with more favourable efficacy- safety profile and reduced need for monitoring could improve the feasibility of extended anticoagulation. PMID:24846227

Becattini, Cecilia; Manina, Giorgia



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

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 ?mol 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 five different L-arginine-degrading pathways are present in the investigated cyanobacterial species. In Synechocystis sp. PCC 6803 an L-arginine deiminase pathway and an L-arginine oxidase/dehydrogenase pathway represent the major pathways, while the L-arginine decarboxylase pathway most likely only functions in polyamine biosynthesis. The transcripts encoding the enzymes of the two major pathways were constitutively expressed with the exception of the transcript for the carbamate kinase, which was substantially up-regulated in cells grown with L-arginine.

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



Regulation of L-arginine transport and nitric oxide release in superfused porcine aortic endothelial cells.  

PubMed Central

1. We have investigated whether changes in extracellular ion composition and substrate deprivation modulate basal and/or bradykinin-stimulated L-arginine transport and release of nitric oxide (NO) and prostacyclin (PGI2) in porcine aortic endothelial cells cultured and superfused on microcarriers. 2. Saturable L-arginine transport (Km = 0.14 +/- 0.03 mM; Vmax = 2.08 +/- 0.54 nmol min-1 (5 x 10(6) cells)-1) was pH insensitive and unaffected following removal of extracellular Na+ or Ca2+. 3. Cationic arginine analogues, including L-lysine and L-ornithine, inhibited L-arginine transport, whilst 2-methylaminoisobutyric acid, beta-2-amino-bicyclo[2,2.1]-heptane-2-carboxylic acid, L-phenylalanine, 6-diazo-5-oxo-norleucine, L-glutamine, L-cysteine and L-glutamate were poor inhibitors. 4. Deprivation of L-arginine (30 min to 24 h) reduced intracellular free L-arginine levels from 0.87 +/- 0.07 to 0.40 +/- 0.05 mM (P < 0.05) and resulted in a 40% stimulation of L-arginine, L-lysine and L-ornithine transport. 5. L-arginine and NG-monomethyl-L-arginine (L-NMMA), but not N omega-nitro-L-arginine methyl ester (L-NAME), trans-stimulated efflux of L-[3H]arginine. 6. Depolarization of endothelial cells with 70 mM K+ reduced L-arginine influx and prevented the stimulation of transport by 100 nM bradykinin, but agonist-induced release of NO and PGI2 was still detectable. 7. Basal rates of L-arginine transport and NO release were unaffected during superfusion of cells with a nominally Ca(2+)-free solution. Bradykinin-stimulated L-arginine transport was insensitive to removal of Ca2+, whereas agonist-induced NO release was abolished. 8. Although bradykinin-stimulated NO release does not appear to be coupled directly to the transient increase in L-arginine transport, elevated rates of L-arginine influx via system y+ in response to agonist-induced membrane hyperpolarization or substrate deprivation provide a mechanism for enhanced L-arginine supply to sustain NO generation. Images Figure 6

Bogle, R G; Baydoun, A R; Pearson, J D; Mann, G E



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


Thin films containing casein appear to be a promising material for coatings used in the medical area to promote biomineralization. ?- and ?-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 ?-casein were slightly thicker than ones with ?-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. PMID:24703671

Szyk-Warszy?ska, Lilianna; Kilan, Katarzyna; Socha, Robert P



Synthesis and Characterization of Chemical Analogs of L-Arginine Phosphate.  

National Technical Information Service (NTIS)

L-arginine phosphate is a promising new material for harmonic generation of the Nd:YAG fundamental wavelength, 1064 nm. The synthesis of 24 other salts of L-arginine was attempted and millimeter size crystals of 9 of these were obtained. These were analyz...

S. B. Monaco L. D. Davis S. P. Velsko F. T. Wang D. Eimerl



l-Arginine promotes capacitation and acrosome reaction in cryopreserved bovine spermatozoa  

Microsoft Academic Search

Sperm capacitation and acrosome reaction are essential for fertilization and they are considered as part of an oxidative process involving superoxide and hydrogen peroxide. In human spermatozoa, the amino acid l-arginine is a substrate for the nitric oxide synthase (NOS) producing nitric oxide (NO), a reactive molecule that participates in capacitation as well as in acrosome reaction. l-Arginine plays an

Cristian O'Flaherty; Pablo Rodriguez; Sudha Srivastava



Antioxidant activity of simvastatin prevents L-arginine-induced acute toxicity of pancreas  

PubMed Central

L-arginine is a semi-essential amino acid that found naturally in food. It has been shown that administration of large doses of L-arginine can induce acute pancreatitis. In the present study, we evaluated if simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, might prevent acute pancreatitis induced by L-arginine. Thirty male Wistar rats were randomly allocated to five groups. Groups were: DMSO, saline, simvastatin, L-arginine, and simvastatin with L-arginine. Twenty four hours after the last dose, rats were sacrificed and their blood was collected from heart for biochemical analysis. Pancreatic tissues were obtained for analysis of glutathione peroxidase (GPx), glutathione s-transferase (GST), lipid peroxide levels (MDA) and histology analysis was examined for pancreas. Results indicated that treatment with simvastatin significantly enhanced levels of GPx and GST and decreased lipid peroxide levels induced by L-arginine compared to the vehicle. Moreover, histopathological analysis further confirmed that administration of simvastatin relatively prevented pancreatic acinar cell damage compared to those animals received L-arginine alone. These findings pointed out the protective role of simvastatin against acute pancreatitis induced by high doses of L-arginine.

Matalka, Ismail I; Mhaidat, Nizar M; Fatlawi, Lina A



Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis  

Microsoft Academic Search

BACKGROUND: L-arginine is the common substrate for nitric oxide synthases and arginases. Increased arginase levels in the blood of patients with cystic fibrosis may result in L-arginine deficiency and thereby contribute to low airway nitric oxide formation and impaired pulmonary function. METHODS: Plasma amino acid and arginase levels were studied in ten patients with cystic fibrosis before and after 14

Hartmut Grasemann; Raphael Schwiertz; Corinna Grasemann; Udo Vester; Kurt Racké; Felix Ratjen



Malaria-Associated l-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia  

PubMed Central

Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop l-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of l-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with l-arginine or l-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with l-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing l-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans.

Chau, Jennifer Y.; Tiffany, Caitlin M.; Nimishakavi, Shilpa; Lawrence, Jessica A.; Pakpour, Nazzy; Mooney, Jason P.; Lokken, Kristen L.; Caughey, George H.; Tsolis, Renee M.



Naringenin adds to the protective effect of l-arginine in monocrotaline-induced pulmonary hypertension in rats: Favorable modulation of oxidative stress, inflammation and nitric oxide.  


The present study was directed to investigate the possible modulatory effect of naringenin when co-administered with l-arginine in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). l-arginine (500mg/kg) and naringenin (50mg/kg) were orally administered daily, alone and in combination, for 3weeks. Mean arterial blood pressure, electrocardiography and echocardiography were then recorded and rats were sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Combined therapy provided a significant improvement in l-arginine protective effect toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline treatment. Furthermore, combined therapy prevented monocrotaline-induced changes in endothelial and inducible nitric oxide synthase protein expression as well as histological analysis compared with either treatment alone. In conclusion, naringenin significantly adds to the protective effect of l-arginine in pulmonary hypertension induced by monocrotaline in rats. PMID:24878387

Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M



Nucleation studies of ZTC doped with L-arginine in supersaturated aqueous solutions  

NASA Astrophysics Data System (ADS)

The metastable zonewidth studies are carried out for various temperatures for supersaturated aqueous solutions of zinc thiourea chloride added with 1 mole % of L-arginine. The metastable zonewidth is increased with the addition of L-arginine. The induction period is experimentally determined and various critical nucleation parameters such as radius of critical nucleus, number of molecules in the critical nucleus, critical free energy of nucleus and interfacial tension are also calculated based on the classical theory for homogeneous crystal nucleation. The induction period is increased with the increase of L-arginine addition. The critical nucleation parameters vary with increase in doping concentration. It is also observed that the nucleation rate increases with the increase of supersaturation. The second harmonic generation (SHG) efficiency measurements are carried out with different doping concentration of L-arginine reveal that nonlinear optical (NLO) property is enhanced by L-arginine dopant.

Balu, T.; Rajasekaran, T. R.; Murugakoothan, P.



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


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. PMID:12736155

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



Long-term testing  

SciTech Connect

Land-based gas turbines are significantly different from automotive gas turbines in that they are designed to operate for 50,000 h or greater (compared to 5,000--10,000 h). The primary goal of this research is to determine the long-term survivability of ceramic materials for industrial gas turbine applications. Research activities in this program focus on the evaluation of the static tensile creep and stress rupture (SR) behavior of three commercially available structural ceramics which have been identified by the gas turbine manufacturers as leading candidates for use in industrial gas turbines. For each material investigated, a minimum of three temperatures and four stresses will be used to establish the stress and temperature sensitivities of the creep and SR behavior. Because existing data for many candidate structural ceramics are limited to testing times less than 2,000 h, this program will focus on extending these data to times on the order of 10,000 h, which represents the lower limit of operating time anticipated for ceramic blades and vanes in gas turbine engines. A secondary goal of the program will be to investigate the possibility of enhancing life prediction estimates by combining interrupted tensile SR tests and tensile dynamic fatigue tests in which tensile strength is measured as a function of stressing rate. The third goal of this program will be to investigate the effects of water vapor upon the SR behavior of the three structural ceramics chosen for the static tensile studies by measuring the flexural strength as a function of stressing rate at three temperatures.

Ferber, M.; Graves, G.A. Jr.



Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group.  


The use of long-term oral anticoagulant treatment after myocardial infarction remains controversial because of conflicting findings on mortality in previous trials and the increased risk of bleeding associated with anticoagulants. We have carried out a randomised, placebo-controlled, double-blind, multicentre trial in 3404 hospital survivors of myocardial infarction. Eligible patients were randomly assigned to anticoagulant (nicoumalone or phenprocoumon) or placebo treatment within 6 weeks of discharge. The target prothrombin time was 2.8-4.8 international normalised ratio. During mean follow-up of 37 (range 6-76) months there were 170 deaths among 1700 anticoagulant-treated patients and 189 in 1704 placebo-treated patients (hazard ratio 0.90 [95% CI 0.73-1.11]). Anticoagulant treatment led to significant reductions by comparison with placebo treatment in recurrent myocardial infarction (114 vs 242 patients; hazard ratio 0.47 [0.38-0.59]) and cerebrovascular events (37 vs 62; 0.60 [0.40-0.90]). Major bleeding complications were seen in 73 patients who received anticoagulants and 19 who received placebo. We conclude that long-term oral anticoagulant treatment after myocardial infarction in low-risk patients has a limited effect on mortality but achieves substantial benefit by reducing the risk of cerebrovascular events and recurrent myocardial infarction. PMID:7906757



Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in metastatic colorectal cancer.  

PubMed Central

In a phase I study of weekly administered cisplatin combined with oral etoposide, we observed a partial response in 4 out of 11 patients with metastatic colorectal cancer. Subsequently, we performed a phase II study to investigate the activity of this combination as first-line treatment in this disease. Fourteen patients with metastatic colorectal cancer were enrolled in this study. Treatment consisted of cisplatin, administered in 3% sodium chloride, at a dose of 70 mg m-2 on days 1, 8 and 15 and days 29, 36 and 43 combined with oral etoposide 50 mg absolute dose daily on days 1-15 of both courses. Patients with stable disease or better continued treatment with etoposide 50 mg m-2 orally on days 1-21 every 28 days. A partial response was observed in two patients with liver metastases (14%; 95% confidence limits 2-42%) for 30 and 32 weeks. Five patients had stable disease. Toxicity consisted mainly of anaemia, leucocytopenia, nausea and vomiting. Tinnitus was reported by six patients. The activity of the combination cisplatin-oral etoposide in the schedule is only minimal in metastatic colorectal cancer.

Planting, A. S.; van der Burg, M. E.; van den Bent, M. J.; de Boer-Dennert, M.; Stoter, G.; Verweij, J.



Long-Term Exposure to Oral Methylphenidate or dl-Amphetamine Mixture in Peri-Adolescent Rhesus Monkeys: Effects on Physiology, Behavior, and Dopamine System Development  

PubMed Central

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 (BPND), an index of tracer-specific binding, and amphetamine-induced changes in BPND 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.

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



Endothelium-dependent vasodilation is independent of the plasma L-arginine\\/ADMA ratio in men with stable angina  

Microsoft Academic Search

OBJECTIVESThis study was designed to determine the effect of two weeks’ treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina.BACKGROUNDThe ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been

Hamish A Walker; Elaine McGing; Ian Fisher; Rainer H Böger; Stefanie M Bode-Böger; Graham Jackson; James M Ritter; Philip J Chowienczyk



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


Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus. PMID:23026748

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



L-arginine transport is increased in macrophages generating nitric oxide.  

PubMed Central

Transport of L-arginine and nitrite production were examined in the murine macrophage cell line J774. Bacterial lipopolysaccharide (LPS) induced a dose- and time-dependent stimulation of nitrite production, which was further increased in the presence of interferon-gamma. Nitrite synthesis was absolutely dependent on extracellular L-arginine and inhibited in the presence of L-lysine or L-ornithine. In unactivated J774 cells L-arginine transport was saturable, with an apparent Km of 0.14 +/- 0.04 mM and Vmax. of 15 +/- 2 nmol/h per 10(6) cells. LPS (1 microgram/ml) induced a time-dependent stimulation of L-arginine transport, and after 24 h the Vmax. increased to 34 +/- 2 nmol/h per 10(6) cells. These findings indicate that activation of J774 cells with LPS produces an increase in both L-arginine transport and nitrite synthesis. The elevated rate of L-arginine transport in activated J774 cells may provide a mechanism for sustained substrate supply during enhanced utilization of L-arginine for the generation of NO.

Bogle, R G; Baydoun, A R; Pearson, J D; Moncada, S; Mann, G E



Transplantation-associated long-term immunosuppression promotes oral colonization by potentially opportunistic pathogens without impacting other members of the salivary bacteriome.  


Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. PMID:23616410

Diaz, Patricia I; Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna



Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials  

PubMed Central

Summary Background Bisphosphonates might modulate the development of symptomatic bone metastases in men with prostate cancer. The Medical Research Council (MRC) PR05 and PR04 randomised controlled trials assessed the use of sodium clodronate, an oral, first-generation bisphosphonate. We report the final analyses of long-term survival data with additional follow-up in both trials. Methods 311 men with metastatic disease were recruited to PR05 between 1994 and 1998, and 508 men with non-metastatic disease were recruited to PR04 from 1994 to 1997. All men were treated according to the recruiting site's standard practice at the time: for metastatic disease, all men were starting or responding to long-term hormone therapy; for non-metastatic disease, most men had radiotherapy, hormone therapy, or both. Men were randomly assigned to take four tablets per day of sodium clodronate (2080 mg) or matching placebo for up to 3 years (metastatic disease) or 5 years (non-metastatic). Long-term overall survival was assessed on an intention-to-treat basis in all men at sites in England and Wales using data from the National Health Service Information Centre, which held data for 278 of 311 men in the PR05 trial and 471 of 508 men in the PR04 trial. These studies are registered International Standardised Randomised Controlled Trials, numbers ISRCTN38477744 (PR05) and ISRCTN61384873 (PR04). Findings Of the 278 men with metastatic disease, 258 (93%) were reported to have died. Evidence of a benefit for those with metastatic disease from use of sodium clodronate compared with placebo was seen in overall survival (hazard ratio [HR] 0·77, 95% CI 0·60–0·98; p=0·032). Of the 471 men with non-metastatic disease, 281 (60%) were reported to have died, with no evidence of improvement in overall survival with clodronate compared with placebo (HR 1·12, 0·89–1·42; p=0·94). Interpretation Long-term data from these trials show that a first-generation bisphosphonate, sodium clodronate, improves overall survival in men with metastatic prostate cancer who are starting hormone therapy, but there is no evidence of an effect in men with non-metastatic prostate cancer. Funding UK MRC; and an education grant and free drug from Roche Products Ltd.

Dearnaley, David P; Mason, Malcolm D; Parmar, Mahesh KB; Sanders, Karen; Sydes, Matthew R



Presynaptic long-term plasticity  

PubMed Central

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.

Yang, Ying; Calakos, Nicole



Treatment of oral pemphigoid with intravenous immunoglobulin as monotherapy. Long-term follow-up: influence of treatment on antibody titres to human ?6 integrin  

PubMed Central

Oral pemphigoid (OP) is a chronic autoimmune disease, involving the oral cavity, characterized by a homogenous linear deposition of immunoglobulins, complement, or both along the basement membrane zone (BMZ) and a subepithelial blister formation. The ?6/?4 heterodimer is an integrin family of adhesion receptors, which mediates basal cell to matrix interactions. Recent evidence suggests a pathophysiologic role for antibodies against human ?6 integrin in blister formation in OP, in organ culture studies. Fifty percent of OP patients have been reported to experience disease progression to involve other mucosal tissues, including the eye and larynx. To prevent this extension of disease, systemic therapy with systemic corticosteroids, dapsone, and immunosuppressive agents has been recommended. The use of intravenous immunoglobulin (IVIg) in the treatment of pemphigoid has been recently described. In this study, we present the use of IVIg, in a group of seven patients, with severe OP, in whom systemic conventional treatment was contraindicated. To determine the influence of treatment on antibodies to human ?6 integrin in OP, seven patients with OP treated with IVIg therapy and a comparable control group of seven patients with OP, treated with conventional therapy, were evaluated at monthly intervals, for a 12 consecutive month treatment period. An effective clinical response was observed in all seven patients treated with IVIg therapy, after a mean treatment period of 4·5 months. IVIg therapy induced a prolonged and sustained clinical remission in all seven patients after a mean treatment period of 26·9 months. A statistically significant difference was observed in the quality of life pre- and post-IVIg therapy (P < 0·001). Both the study and the control groups had a very similar initial serological response to treatment. A statistically significant reduction in the antibody titres was observed after four months of treatment, in both groups (P = 0·015). Thereafter, patients treated with IVIg therapy had a faster rate of decline in the antibody titres, and the difference in the rate of decline between the study and control groups became statistically significant after six months of treatment (P = 0·03). The use of IVIg therapy resulted in reduction of anti?6 antibody titres and in inducing and maintaining both a sustained, clinical and serological remission.

Sami, N; Bhol, K C; Ahmed, A R



Synthesis, crystal structure and vibrational spectroscopy of a nonlinear optical crystal: L-arginine maleate dihydrate  

NASA Astrophysics Data System (ADS)

From the aqueous solution containing L-arginine and maleic acid (C 4H 4O 4), crystals of L-arginine maleate dihydrate were grown. The crystal structure was determined by single crystal X-ray diffraction. In the triclinic unit cell (space group P1), the molecule contains one L-arginine cation, one maleate anion and two water molecules. The crystal can be described as an inclusion complex from its layer structure. The basic unit in L-arginine layer is centrosymmetric and the maleate anions exist in coplanarity. Hydrogen bond plays a great role in the construction of the crystal and nonlinear optical properties. The crystal was characterized by infrared (IR) and Raman spectra. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) were used to study its thermal properties. Powder second harmonic generation (SHG) experiment was investigated to explore its NLO properties.

Sun, Z. H.; Yu, W. T.; Cheng, X. F.; Wang, X. Q.; Zhang, G. H.; Yu, G.; Fan, H. L.; Xu, D.



L-arginine enhances immunity to parasitoids in Drosophila melanogaster and increases NO production in lamellocytes.  


Drosophila melanogaster was used as a model system to explore the link between nutrition and immunity, and to investigate the role of nitric oxide (NO) in enhancing immunity following dietary enhancement with L-arginine. First, we show that adding L-arginine to the food medium increases the ability of D. melanogaster larvae to encapsulate the eggs of the parasitoid Asobara tabida. Secondly, we show that the increase in immunity is specific to L-arginine, and not to an enhanced calorific content, and that immunity decreases when larvae are fed food with added L-NAME, an inhibitor of nitric oxide synthase. Finally, we show that parasitised larvae fed L-arginine have increased haemocyte numbers, and that the lamellocytes (haemocytes which play a key role in encapsulation) show evidence of an increased production of NO. These results suggest that NO plays a key role in immunity and that the effect of NO is mostly targeted via the lamellocytes. PMID:21527285

Kraaijeveld, Alex R; Elrayes, Naji P; Schuppe, Hansjürgen; Newland, Philip L



Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach  

PubMed Central

The combination of oral melphalan and dexamethasone is considered standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation. However, previous trials reported different rates of response and survival, mainly because of the different proportions of high-risk patients. In the present study, including a total of 259 subjects, we treated 119 patients with full-dose melphalan and dexamethasone (dexamethasone 40 mg days 1–4), and 140 patients with advanced cardiac disease with an attenuated dexamethasone schedule (20 mg). Hematologic response rates were 76% in the full-dose group and 51% in the patients receiving the attenuated schedule; the corresponding complete response rates were 31% and 12%, respectively. The median survival was 7.4 years in the full-dose group and 20 months in the attenuated-dose group. Use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy were independent prognostic determinants. In relapsed/refractory subjects bortezomib combinations granted high hematologic response rates (79% and 63%, respectively), proving the most effective rescue treatment after melphalan and dexamethasone. In summary, melphalan plus dexamethasone was highly effective with minimal toxicity, confirming its central role in the treatment of AL amyloidosis. Future randomized trials will clarify whether bortezomib is best used in frontline combination with melphalan and dexamethasone or as rescue treatment.

Palladini, Giovanni; Milani, Paolo; Foli, Andrea; Obici, Laura; Lavatelli, Francesca; Nuvolone, Mario; Caccialanza, Riccardo; Perlini, Stefano; Merlini, Giampaolo



L-arginine stimulates insulin secretion from the pancreas of normal and diabetic rats  

Microsoft Academic Search

Summary.   Several reports have shown that nitric oxide (NO) stimulates glucose-induced insulin secretion in the pancreas of normal\\u000a rat but the effect of L-arginine (a NO donor) on insulin secretion from the pancreas of diabetic pancreas is unknown. Fragments\\u000a of pancreatic tissue from normal and diabetic rats were incubated for 45 min in Krebs solution containing 100 mM L-arginine.\\u000a The

E. Adeghate; A. S. Ponery; T. El-Sharkawy; H. Parvez



[Correction of endothelial dysfunction by L-arginine under experimental pre-eclampsia conditions].  


The ADMA-like pre-eclampsia in pregnant rats was modeled by daily introduction of L-NAME in a dose of 25 mg/kg for 7 days. L-arginine (200 mg/kg) prevented the development of arterial hypertension and a decrease in placentary microcirculation and microalbuminuria. The possibility of using L-arginine for the prevention of competitive eNOS inhibition by ADMA is discussed. PMID:22550853

Pokrovski?, M V; Pokrovskaia, T G; Gureev, V V; Barsuk, A A; Proskuriakova, E V; Korokin, M V; Gudyrev, O S; Belous, A S; Kochkarov, V I; Danilenko, L M; Levashova, O V; Mal'tseva, N V; Polianskaia, O S



L-Arginine Reactivity in Cerebral Vessels After Severe Traumatic Brain Injury  

PubMed Central

Objectives Traumatic brain injury (TBI) causes an early reduction of cerebral blood flow (CBF). The purpose was to study cerebrovascular endothelial function by examining the reactivity of cerebral vessels to L-arginine. Methods Fifty-one patients with severe TBI were prospectively studied by measuring cerebral hemodynamics before and after the administration of L-arginine, 300 mg/kg at 12 hrs and at 48 hrs after injury. These hemodynamic measurements, using transcranial Doppler techniques, included internal carotid flow volume as an estimate of hemispheric cerebral blood flow, flow velocity in intracranial vessels, CO2 reactivity, and dynamic pressure autoregulation using thigh cuff deflation and carotid compression methods. Changes in the hemodynamics with L-arginine administration were analyzed using a general linear mixed model. Results L-arginine produced no change in mean arterial pressure, intracranial pressure, or brain oxygenation. Overall, L-arginine induced an 11.3% increase in internal carotid artery flow volume (p= .0190). This increase was larger at 48 hrs than at 12 hrs (p= .0045), and tended to be larger in the less injured hemisphere at both time periods. The response of flow velocity in the intracranial vessels was similar, but smaller differences with administration of L-arginine were observed. There was a significant improvement in CO2 reactivity with L-arginine, but no change in dynamic pressure autoregulation. Discussion The low response of the cerebral vessels to L-arginine at 12 hrs post-injury with improvement at 48hrs suggests that dysfunction of cerebrovascular endothelium plays a role in the reduced CBF observed after TBI.

Rangel-Castilla, Leonardo; Ahmed, Osama; Goodman, J. Clay; Gopinath, Shankar; Valadka, Alex; Robertson, Claudia



Macrophage Cytotoxicity: Role for L-Arginine Deiminase and Imino Nitrogen Oxidation to Nitrite  

Microsoft Academic Search

Previous studies have shown that cytotoxic activated macrophages cause inhibition of DNA synthesis, of mitochondrial respiration, and of aconitase activity in tumor target cells. An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is now shown to cause this pattern of metabolic inhibition. Murine cytotoxic activated macrophages synthesize L-citrulline and nitrite in the presence of L-arginine

John B. Hibbs; Read R. Taintor; Zdenek Vavrin



Supplemental l-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury  

Microsoft Academic Search

Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor l-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs,

Hiroki Sato; Zhi-Qing Zhao; D. Scott McGee; Mark W. Williams; John W. Hammon; J. Vinten-Johansen



L-Arginine Availability Modulates Local Nitric Oxide Production and Parasite Killing in Experimental Trypanosomiasis  

Microsoft Academic Search

Nitric oxide (NO) is an important effector molecule of the immune system in eliminating numerous pathogens. Peritoneal macrophages from Trypanosoma brucei brucei-infected mice express type II NO synthase (NOS-II), produce NO, and kill parasites in the presence of L-arginine in vitro. Nevertheless, parasites proliferate in the vicinity of these macrophages in vivo. The present study shows that L-arginine availability modulates




Vascular Effects of l-Arginine: Anything beyond a Substrate for the NO-Synthase?  

Microsoft Academic Search

L-arginine supplementation is hypothesized to reduce endothelial dysfunction and atherogenesis via increased biosynthesis of nitric oxide. Here we describe superoxide scavenging properties of arginine as an additional aspect which needs to be considered. Furthermore, arginine reduced copper-induced lipid peroxidation, indicating that superoxide anions essentially contribute to this process. In intact endothelial cells, L-arginine but not D-arginine diminished superoxide release and

Thomas C. Wascher; Karla Posch; Sandra Wallner; Albin Hermetter; Gert M. Kostner; Wolfgang F. Graier



L-Arginine enhances aerobic exercise capacity in association with augmented nitric oxide production  

Microsoft Academic Search

L-Arginine enhances aerobic exercise capacity in association with augmented nitric oxide production. J Appl Physiol 90: 933-938, 2001.—We tested whether supplementation with L-arginine can augment aerobic capacity, particularly in con- ditions where endothelium-derived nitric oxide (EDNO) ac- tivity is reduced. Eight-week-old wild-type (E 1 ) and apoli- poprotein E-deficient mice (E 2 ) were divided into six groups; two groups




Vascular endothelial dysfunction resulting from l-arginine deficiency in a patient with lysinuric protein intolerance  

PubMed Central

Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the gene (5.3-kbp Alu-mediated deletion, IVS3+1G??). The lumen diameter of the brachial artery was measured in this patient and in healthy controls at rest, during reactive hyperemia (endothelium-dependent vasodilation [EDV]), and after sublingual nitroglycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NOx concentrations were markedly reduced in the patient compared with those for the controls. They became normal after an L-arginine infusion. EIV was not significantly different between the patient and controls. Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. Thus, in the LPI patient, L-arginine deficiency caused vascular endothelial dysfunction via a decrease in NO production.

Kamada, Yoshihiro; Nagaretani, Hiroyuki; Tamura, Shinji; Ohama, Tohru; Maruyama, Takao; Hiraoka, Hisatoyo; Yamashita, Shizuya; Yamada, Akira; Kiso, Shinichi; Inui, Yoshiaki; Ito, Nobuyuki; Kayanoki, Yoshiro; Kawata, Sumio; Matsuzawa, Yuji



Basics (Long-Term Care)  


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BHT, Long-Term Toxicity.  

National Technical Information Service (NTIS)

The Chemical Manufacturers Association (CMA) recently received preliminary results of a long-term toxicity study on butylated hydroxytoluene (BHT) in rats. The study was conducted by the Institute of Toxicology, National Food Institute of Denmark. Prelimi...



Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate  

SciTech Connect

Previous studies have shown that murine macrophages immunostimulated with interferon ..gamma.. and Escherichia coli lipopolysaccharide synthesize NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated RAW 264.7 cells and was totally absent in unstimulated cells. This activity requires NADPH and L-arginine and is enhanced by Mg/sup 2 +/. When the subcellular fraction containing the enzyme activity was incubated with L-arginine, NADPH, and Mg/sup 2 +/, the formation of nitric oxide was observed. Nitric oxide formation was dependent on the presence of L-arginine and NADPH and was inhibited by the NO/sub 2//sup -//NO/sub 3//sup -/ synthesis inhibitor N/sup G/-monomethyl-L-arginine. Furthermore, when incubated with L-(guanido-/sup 15/N/sub 2/)arginine, the nitric oxide was /sup 15/N-labeled. The results show that nitric oxide is an intermediate in the L-arginine to NO/sub 2//sup -/, NO/sub 3//sup -/, and citrulline pathway. L-Arginine is required for the activation of macrophages to the bactericidal/tumoricidal state and suggests that nitric oxide is serving as an intracellular signal for this activation process in a manner similar to that very recently observed in endothelial cells, where nitric oxide leads to vascular smooth muscle relaxation.

Marletta, M.A.; Yoon, P.S.; Iyengar, R.; Leaf, C.D.; Wishnok, J.S.



Pharmacokinetics of L-arginine in adults with moderately severe malaria.  


Severe malaria is associated with decreased nitric oxide (NO) production and low plasma concentrations of L-arginine, the substrate for NO synthase. Supplementation with L-arginine has the potential to improve NO bioavailability and outcomes. We developed a pharmacokinetic model for L-arginine in moderately severe malaria to explore the concentration-time profile and identify important covariates. In doses of 3, 6, or 12 g,L-arginine was infused over 30 min to 30 adults with moderately severe malaria, and plasma concentrations were measured at 8 to 11 time points. Patients who had not received L-arginine were also assessed and included in the model. The data were analyzed using a population approach with NONMEM software. A two-compartment linear model with first-order elimination best described the data, with a clearance of 44 liters/h (coefficient of variation [CV] = 52%) and a volume of distribution of 24 liters (CV = 19%). The natural time course of L-arginine recovery was described empirically by a second-order polynomial with a time to half recovery of 26 h. The half-life of exogenous L-arginine was reduced in patients with malaria compared with that for healthy adults. Weight and ethnicity were significant covariates for clearance. MATLAB simulations of dosing schedules for use in future studies predicted that 12 g given over 6, 8, or 12 h will provide concentrations above the K(m) of endothelial cell CAT-1 transporters in 90%, 75%, and 60% of patients, respectively. PMID:18838585

Yeo, Tsin W; Rooslamiati, Indri; Gitawati, Retno; Tjitra, Emiliana; Lampah, Daniel A; Kenangalem, Enny; McNeil, Yvette R; Price, Richard N; Anstey, Nicholas M; Duffull, Stephen B



Identification of inhibitors of nitric oxide synthase that do not interact with the endothelial cell L-arginine transporter.  

PubMed Central

The effects of inhibitors of nitric oxide (NO) synthase and other cationic amino acids on unidirectional L-arginine transport were studied in porcine aortic endothelial cells cultured in microwell plates or perfused in microcarrier columns. L-Homoarginine, L-lysine and L-ornithine inhibited transport of L-arginine. The NO synthase inhibitors NG-monomethyl-L-arginine and NG-iminoethyl-L-ornithine also reduced L-arginine uptake, whereas NG-nitro-L-arginine and its methyl-ester had no inhibitory effect. The ability to modulate selectively endothelial cell L-arginine transport or NO synthase activity will allow further characterization of the arginine transporter and its role in regulating NO biosynthesis.

Bogle, R. G.; Moncada, S.; Pearson, J. D.; Mann, G. E.



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

SciTech Connect

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

Arjunan, S. [Department of Physics, Panimalar Engineering College, Chennai 602103 (India); Department of Physics, Presidency College, Chennai 600005 (India); Mohan Kumar, R. [Crystal Growth Centre, Anna University, Chennai 600025 (India); Mohan, R. [Department of Physics, Presidency College, Chennai 600005 (India); Jayavel, R. [Crystal Growth Centre, Anna University, Chennai 600025 (India)], E-mail:



Reduced L-arginine level and decreased placental eNOS activity in preeclampsia.  


Nitric oxide is produced enzymatically by the nitric oxide synthase (NOS), which converts L-arginine in the presence of oxygen to L-citrulline and NO. Moreover, it has been reported that asymmetric dimethylarginine (ADMA) acts as is an endogenous inhibitor of endothelial NOS (eNOS) by competing with the enzyme for L-arginine. In this study, we measured L-arginine and ADMA in normal and preeclamptic women, and also investigated the association between the Glu298Asp eNOS gene polymorphism and preeclampsia. Finally, we assessed eNOS expression levels in the placentas of both normal and preeclamptic patients, using Western blot and immunohistochemistry. L-arginine levels were found to be significantly lower in the preeclamptic women than in the normal pregnant women (p=0.02) but there were no significant differences in ADMA levels between the normal and preeclamptic women. We also determined there to be no association between the Glu298Asp eNOS gene and preeclampsia. With regard to placental eNOS expression, we detected a lower degree of eNOS expression in the preeclamptic syncytiotrophoblasts than in the normal syncytiotrophoblasts. We suggest that reduced L-arginine levels, rather than increased ADMA levels, contribute to the development of preeclampsia, and also that decreased placental eNOS expression constitutes a characteristic finding in preeclamptic placentas. PMID:16009421

Kim, Y J; Park, H S; Lee, H Y; Ha, E H; Suh, S H; Oh, S K; Yoo, H-S



Enhanced permeation of methotrexate in vitro by ion pair formation with L-arginine.  


Ion paired solutions of methotrexate in L-arginine/water/propylene glycol systems were evaluated for their potential to enhance the permeation of methotrexate across rabbit nasal mucosa in vitro. The partition coefficient of methotrexate in the methotrexate: L-arginine ion paired systems was observed to be 24 times greater than that of the methotrexate system without L-arginine. The ion pair formation between methotrexate and L-arginine was confirmed by a decrease in the conductivity of the systems in the presence of propylene glycol, a dielectric constant reducing agent. The permeation of methotrexate across the rabbit nasal mucosa from the ion paired systems was observed to be significantly greater (p < 0.05) as compared to control systems of methotrexate solution in water and a sodium salt. Furthermore, a threefold increase in the flux of methotrexate was observed when propylene glycol was added to the ion paired systems. These results suggest that methotrexate: L-arginine ion paired systems have potential in improving the permeation of methotrexate across rabbit nasal mucosa and may form the basis for further development of an intranasal therapeutic system of methotrexate. PMID:19117046

Ivaturi, Vijay D; Kim, S Kwonho



Multiple antioxidants and L-arginine modulate inflammation and dyslipidemia in chronic renal failure rats.  


The kidney is an important source of L-arginine, the endogenous precursor of nitric oxide (NO). Surgical problems requiring extensive renal mass reduction (RMR) decrease renal NO production, leading to multiple hemodynamic and homeostatic disorders manifested by hypertension, oxidative stress, and increased inflammatory cytokines. Using the RMR model of chronic renal failure (CRF), we assessed the effects of twelve weeks' administration of L-arginine and/or a mixture of antioxidants (L-carnitine, catechin, vitamins E and C) on plasma cytokines, soluble intercellular adhesion molecule-1 (sICAM-1), nitrate and nitrites (NO(2)/NO(3)), lipid profile, blood pressure, and renal function. CRF rats showed increased plasma IL-1 alpha, IL1-beta, IL-6, TNF-alpha, and sICAM-1 levels and decreased anti-inflammatory cytokines IL-4 and 10 levels, hypertension, and dyslipidemia. L-arginine treatment improved kidney functions, decreased systolic blood pressure, and decreased inflammatory cytokines levels. Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels and increased IL-4 levels. Combined use of both L-arginine and the antioxidant mixture were very effective in their tendency to recover normal values of kidney functions, plasma cytokines, sICAM-1, blood pressure, NO(2)/NO(3), cholesterol, and triglycerides concentrations. Indeed, the effects of L-arginine and the antioxidants on the reduction of proinflammatory cytokines may open new perspectives in the treatment of uremia. PMID:20199183

Korish, Aida A



Mechanism of Allosteric Inhibition of N-Acetyl-L-glutamate Synthase by L-Arginine  

SciTech Connect

N-Acetylglutamate synthase (NAGS) catalyzes the first committed step in L-arginine biosynthesis in plants and micro-organisms and is subject to feedback inhibition by L-arginine. This study compares the crystal structures of NAGS from Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with L-arginine bound and in the active R-state complexed with CoA and L-glutamate. Under all of the conditions examined, the enzyme consists of two stacked trimers. Each monomer has two domains: an amino acid kinase (AAK) domain with an AAK-like fold but lacking kinase activity and an N-acetyltransferase (NAT) domain homologous to other GCN5-related transferases. Binding of L-arginine to the AAK domain induces a global conformational change that increases the diameter of the hexamer by {approx}10 {angstrom} and decreases its height by {approx}20{angstrom}. AAK dimers move 5{angstrom} outward along their 2-fold axes, and their tilt relative to the plane of the hexamer decreases by {approx}4{sup o}. The NAT domains rotate {approx}109{sup o} relative to AAK domains enabling new interdomain interactions. Interactions between AAK and NAT domains on different subunits also change. Local motions of several loops at the L-arginine-binding site enable the protein to close around the bound ligand, whereas several loops at the NAT active site become disordered, markedly reducing enzymatic specific activity.

Min, Li; Jin, Zhongmin; Caldovic, Ljubica; Morizono, Hiroki; Allewell, Norma M.; Tuchman, Mendel; Shi, Dashuang (GUW); (Maryland); (GWU); (Georgia)



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


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. PMID:24522477

Hristina, K; Langerholc, T; Trapecar, M



[Platelet aggregation in modulation of the pathway L-arginine-NO in rats with cerebral ischemia].  


Platelet aggregation in the plasma of rats with brain ischemia and modulation of L-arginine-NO pathway were studied in experiments (Born method using analyzer AP 21103AO SOLAR). We used L-arginine and inhibitors of NO-synthase: nonselective inhibitor Nomega-nitro-L-arginine methyl ester, selective inhibitors of neuronal NO-synthase-7-nitro-indazole and selective inhibitor of inducible NO-synthase-S-methylisothiourea. We found that an increase in platelet aggregation in rat plasma observed in both periods is mediated via NO: in an early period of brain ischemia it depends on neuronal NO-synthase and in a late period--on inducible NO-synthase. Moreover, a nonselective inhibitor of all isoforms of NO-synthase (including endothelial NO-synthase) Nomega-nitro-L-arginine methyl ester possesses proaggregant properties. On the other hand, L-arginine in combination with 7-nitro-indazole and S-methylisothiourea induces maximal antiaggregatory effect. These data allows us to suppose that endothelium-derived NO decreases platelet aggregation in brain ischemia-reperfusion in rats. PMID:16408659

Maksimovich, N E



Differential impact of L-arginine deprivation on the activation and effector functions of T cells and macrophages  

Microsoft Academic Search

The metabolism of the amino acid L- arginine is emerging as a crucial mechanism for the regulation of immune responses. Here, we charac- terized the impact of L-arginine deprivation on T cell and macrophage (M) effector functions: We show that whereas L-arginine is required uncondi- tionally for T cell activation, M can up-regulate activation markers and produce cytokines and che-

B.-S. Choi; I. Clara Martinez-Falero; C. Corset; M. Munder; M. Modolell; I. Muller; P. Kropf



The effect of chronic administration of l-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze  

PubMed Central

OBJECTIVE: The present study was carried out to evaluate the effect of l-arginine on the learning and memory of estradiol-treated ovariectomized (OVX) rats. METHODS: Forty-eight rats were divided into six groups: (1) sham, (2) OVX, (3) sham-Est, (4) OVX-Est, (5) sham-Est-LA, and (6) OVX-Est-LA. The animals of the sham-Est and OVX-Est groups were treated by weekly injection of estradiol valerate (2mg/kg). The sham-Est-LA and OVX-Est-LA groups were treated in the same manner but with an additional daily injection of l-arginine (200mg/kg). After eight weeks, animals of all groups were tested in the Morris water maze. The escape latency and path traveled to reach the platform were compared between groups. RESULTS: Time latency and path length in the OVX group were significantly higher than in the sham group (P<0.05). The OVX-Est group had a significantly shorter traveled path length and time latency compared to the OVX group (P<0.001). Time latency and path length in the sham-Est group was significantly higher than in the sham group (P<0.001). Time latency and path length in the OVX-Est-LA group were significantly higher than in the OVX-Est group. CONCLUSIONS: These results allow us to propose that chronic treatment with estradiol enhances the spatial learning and memory of OVX rats, and that long term l-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats.

Hosseini, Mahmoud; Headari, Raheleh; Oryan, Sharbanoo; Hadjzadeh, Mosa Alreza; Saffarzadeh, Fatima; Khazaei, Majid



Optical properties of L-arginine doped potassium dihydrogen phosphate crystals  

NASA Astrophysics Data System (ADS)

Potassium dihydrogen phosphate (KDP) exhibits superior nonlinear-optical properties and it has been exploited for variety of applications. Single crystals of organic nonlinear optical material of pure and L-arginine doped potassium dihydrogen phosphate (KDP) were grown by slow evaporation technique from its aqueous solution. The crystal structures of the grown crystals were determined using powder XRD. The powder X-ray diffraction patterns indicated a single phase with the unit cell parameters being unaltered by doping. Infrared and Raman spectroscopies were employed to study the active doping of potassium dihydrogen phosphate crystals with L-arginine amino acid. IR absorption spectra confirmed that the successful doping of L-arginine was achieved by exhibiting the presence of vibrational lines at 1401 cm-1, 1637 cm-1, 1716 cm-1 and 3127 cm-1. This affirmation is supported with more evidences from FT-Raman measurements

Govani, Jayesh; Manciu, Felicia; Joshi, Mihir; Parikh, Ketan; Dave, Dipak



Synthesis, thermal and nonlinear optical characterization of L-arginine semi-oxalate single crystals  

NASA Astrophysics Data System (ADS)

Optically good quality L-arginine semi-oxalate, an organic nonlinear optical crystal, has been synthesized from aqueous solution by slow evaporation method. Single crystal X-ray diffraction (XRD) analysis reveals that the synthesized L-arginine semi-oxalate crystal possesses triclinic structure with unit cell dimensions as a=5.05A?, b=9.73A?, c=13.12A?, ?=111.030, ?=92.790 and ?=91.910. The Fourier transform infra-red (FTIR) spectroscopy was analyzed and the presence of functional groups of L-arginine semi-oxalate was confirmed. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) studies show that the material is thermally stable up to 1460C and the melting point is 1500C. Kurtz and Perry powder technique confirms that the second harmonic generation (SHG) efficiency is 0.32 times that of standard organic materials urea and KDP.

Vasudevan, P.; Gokulraj, S.; Sankar, S.



Spectroscopic and structural studies of L-arginine doped Potassium Dihydrogen Phosphate crystals  

NASA Astrophysics Data System (ADS)

We report in this study the spectroscopic and structural characterization of standard and L-arginine doped potassium dihydrogen phosphate crystals synthesized by a solution growth technique. The infrared absorption and Raman results demonstrate chemical functionalization between the amino (NH3^+) groups of the organic material and the phosphate units of the inorganic crystals. This affirmation, which also implies the achievement of successful doping, is supported by the existence of extra vibrational lines in the IR and Raman spectra of L-arginine doped potassium dihydrogen phosphate crystals; these vibrational lines exhibit shifting towards lower frequencies as compared with the characteristic bands of L-arginine. Incorporation of the amino acid into the structure of the inorganic material is revealed by X-ray diffraction results also, where the shifting of diffraction lines and the appearance of a new one are observed.

Govani, Jayesh; Botez, Cristian; Durrer, William; Manciu, Felicia



L-arginine metabolism and its impact on host immunity against Leishmania infection  

PubMed Central

Leishmaniasis is a vector-borne disease found in many countries worldwide. The causative agent of the disease, Leishmania spp., lives as an obligate intracellular parasite within mammalian hosts. Since tissue macrophages are major target cells for parasite replication, the outcome of infection depends largely on the activation status of these cells. L-arginine is a crucial amino acid required for both nitric oxide (NO)-mediated parasite killing and polyamine-mediated parasite replication. This review highlights the significance of L-arginine as a factor determining the outcomes of Leishmania infection in vitro and its influences on host immune responses in vivo. Various therapeutic approaches targeting L-arginine metabolic pathways during infections with Leishmania are also discussed.

Wanasen, Nanchaya



Modeling of Long Term Care.  

National Technical Information Service (NTIS)

Long-term care (LTC) refers to services for those who are chronically ill with physical or mental disabilities. This monograph focuses on those people who require government assistance in obtaining such care. It explores the use of modeling and simulation...

M. Katzper



Long Term Illness and Wages  

ERIC Educational Resources Information Center

Long-term illness (LTI) is a more prevalent workplace risk than fatal accidents but there is virtually no evidence for compensating differentials for a broad measure of LTI. In 1990 almost 3.4 percent of the U.K. adult population suffered from a LTI caused solely by their working conditions. This paper provides the first estimates of compensating…

Sandy, Robert; Elliott, Robert R.



Simultaneous Bioanalysis of L-Arginine, L-Citrulline, and Dimethylarginines by LC-MS/MS  

PubMed Central

Purpose L-Arginine (ARG) is converted to nitric oxide (NO) and L-citrulline (CIT) by endothelial nitric oxide synthase which is competitively inhibited by asymmetric dimethylarginine (ADMA). We have developed a liquid chromatography-mass spectrometric method for the simultaneous determination of endogenous ARG, labeled ARG (15N4-ARG), CIT, ADMA, and its inactive isomer, symmetric dimethylarginine (SDMA) in biological samples. Methods Concentrations of unlabeled ARG, 15N4-ARG, CIT, ADMA, and SDMA in EA.hy926 human endothelial cell lysate, cell incubation media, rat plasma or rat urine were measured by hydrophilic-interaction liquid chromatography electrospray tandem mass spectrometry. 13C6-ARG, D4-CIT and D7-ADMA were used as internal standards for ARG, CIT and dimethylarginines, respectively. Results The calibration curves of ARG, 15N4-ARG, CIT, ADMA, and SDMA were linear and independent of several sample matrices. Intra- and inter-day variabilities for the quantification of all the compounds were below 15 % in quality control samples. Application of this method to determine the uptake as well as efflux of these compounds was illustrated through in vitro cell study by exposing human endothelial cells to 15N4-ARG, which allowed the observation of generation of 15N3-CIT and 15N3-ARG in the cell lyate. Use of these isotopes adds insights into the cellular handling of endogenous vs. exogenous ARG. Application of this method for rat plasma and rat urine assays was demonstrated after ARG oral supplementation in rats. Conclusion An LC-MS/MS method was developed to quantify 6 ARG-related compounds simultaneously, utilizing 3 separate internal standards. This assay allows concurrent monitoring of uptake, efflux and metabolic processes when isotope-labeled ARG and CIT are measured, and can be applied for determination of these compounds in rat plasma and rat urine.

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



The Metabolism of L-Arginine and Its Significance for the Biosynthesis of Endothelium-Derived Relaxing Factor: Cultured Endothelial Cells Recycle L- Citrulline to L-Arginine  

Microsoft Academic Search

We have investigated the mechanism by which cultured endothelial cells generate L-arginine (L-Arg), the substrat for the biosynthesis of endothelium-derived relaxing factor. When Arg-depleted endothelial cells were incubated in Krebs' solution for 60 min, L-Arg levels were significantly (9.7-fold) elevated. The generation of L-Arg coincided with a substantial decrease (90%) in intracellular L-glutamine (L-Gln), whereas all other amino acids were

Markus Hecker; William C. Sessa; Hayley J. Harris; Erik E. Anggard; John R. Vane



Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine.  

PubMed Central

1. The dependence on extracellular L-arginine of vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) was studied in vivo in rats infused with LPS and in vitro in endothelium-denuded rat thoracic aortic rings exposed to LPS. 2. Infusion of LPS during 50 min at a dose of 10 mg kg-1 h-1 produced a significant impairment of the pressor effect of noradrenaline, while in tissues collected 60 min after the start of LPS infusion, no significant alteration in either plasma arginine concentration or aortic arginine content was found compared to saline-infused controls (where plasma arginine was 78.5 +/- 7 microM and aortic arginine 394 +/- 124 nmol g-1 tissue). 3. Incubation of isolated, endothelium-denuded aortic rings with LPS (10 micrograms ml-1) in the absence of L-arginine for 4 h at 37 degrees C produced a 6 fold (P < 0.01) rightward shift in the noradrenaline concentration-effect curve compared to polymyxin B (1 micrograms ml-1, a LPS neutralizing agent) and reduced by 15% the maximum observed tension. 4. The presence of L-arginine (100 microM) during the incubation with LPS and throughout the following contraction experiments caused a 15 fold (P < 0.01) increase in the EC50 of noradrenaline and greater depression (45%) of the maximum observed tension compared to polymyxin B-treated controls. Responses in control, non LPS-treated rings were unaffected by the presence of L-arginine. 5. The addition of L-arginine to rings incubated with LPS in the absence of L-arginine and maximally precontracted with noradrenaline (10 microM) induced a dose-dependent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Schott, C. A.; Gray, G. A.; Stoclet, J. C.



Cat2 L-arginine transporter-deficient fibroblasts can sustain nitric oxide production.  


High-output nitric oxide (NO) production by nitric oxide synthase 2 (NOS2) contributes to normal cellular processes and pathophysiological conditions. The transport of L-arginine, the substrate for NOS2, is required for sustained NO production by NOS2. L-Arginine can be transported by several kinetically defined transport systems, although the majority of arginine uptake is mediated by transport system y(+), encoded by the Cat1-3 gene family. Using macrophages from Cat2-deficient mice, we previously determined that arginine uptake via CAT2 is absolutely required for sustained NO production. Because NO production by fibroblasts is important in wound healing, we sought to determine whether CAT2 is required for NO production in cytokine-stimulated Cat2-deficient and wild-type embryonic fibroblasts. Although macrophages and fibroblasts both required extracellular L-arginine for NO production, NO synthesis by activated Cat2(-/-) fibroblasts was reduced only 19%, whereas Cat2(-/-) macrophages were virtually unable to produce NO. As expected, activated Cat2(-/-) fibroblasts had reduced system y(+)-mediated arginine uptake. However, their reduced NO output was not the result of a significant difference in intracellular L-arginine levels following cytokine stimulation. Uptake experiments revealed that the L-arginine transport system y(+)L was the major cationic amino acid carrier in fibroblasts of both genotypes. We conclude that NO production in embryonic fibroblasts is only partially dependent on CAT2 and that other compensating transporters provide arginine for NOS2-mediated NO synthesis. The data demonstrate that fibroblasts and macrophages have differential dependence on CAT2-mediated L-arginine transport for NO synthesis. The important physiological implication of this finding is discussed. PMID:12446172

Nicholson, Benjamin; Manner, Cathyryne K; MacLeod, Carol L



Synthesis and characterization of chemical analogs of L-arginine phosphate  

NASA Astrophysics Data System (ADS)

L-arginine phosphate is a promising new material for generating harmonics of the Nd: YAG fundamental wavelength, 1064 nm. The synthesis of 20 other salts of L-arginine was attempted and millimeter size crystals of 10 of these were obtained. These were analyzed for crystal structure and chemical composition and the linear and nonlinear optical properties were measured. The compounds were all oprically biaxial and several gave second harmonic signals greater than quartz. Phasematching has been observed in four of the crystals to date.

Monaco, S. B.; Davis, L. E.; Velsko, S. P.; Wang, F. T.; Eimerl, D.; Zalkin, A.



Theoretical calculation and vibrational spectral analysis of L-arginine trifluoroacetate  

NASA Astrophysics Data System (ADS)

Fourier transform infrared and Raman spectra of the nonlinear optical crystal, L-arginine trifluoroacetate ( L-arginine·CF 3COOH, abbreviated as LATF) have been calculated by the first-principles calculation and investigated in experiment. The calculated results are slightly different from those experimental values because of the distinction resulted from the intermolecular hydrogen bonds. The role of this type of intermolecular interaction on the crystal vibrational spectra and nonlinear optical properties has been discussed. The absorption-edge on the IR side has been estimated by the theoretical approach on basis of the calculated infrared spectrum, which will be meaningful for further research on NLO crystal.

Sun, Z. H.; Zhang, L.; Xu, D.; Wang, X. Q.; Liu, X. J.; Zhang, G. H.



Synthesis and characterization of chemical analogs of L-arginine phosphate  

SciTech Connect

L-arginine phosphate is a promising new material for harmonic generation of the Nd:YAG fundamental wavelength, 1064 nm. The synthesis of 24 other salts of L-arginine was attempted and millimeter size crystals of 9 of these were obtained. These were analyzed for crystal structure and chemical composition and the linear and nonlinear optical properties measured. The compounds were all optically biaxial and several gave second harmonic signals greater than quartz. Phasematching has been observed in four of the crystals to date. 3 refs., 2 tabs.

Monaco, S.B.; Davis, L.D.; Velsko, S.P.; Wang, F.T.; Eimerl, D.; Zalkin, A.



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


An electrochemical sensor for fluoroquinolones (FQs) based on polymerization of ?-cyclodextrin (?-CD) and L-arginine (L-arg) modified carbon paste electrode (CPE) (P-?-CD-L-arg/CPE) was built for the first time. Synergistic effect of L-arg and ?-CD was used to construct this sensor for quantification of these important antibiotics. Scanning electron microscope (SEM) image shows that polymer of ?-CD and L-arg has been successfully modified on electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) further indicate that polymer of ?-CD and L-arg efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analyte and electrode. Under the optimized conditions, this modified electrode was utilized to determine the concentrations of ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. The differential pulse voltammogram (DPV) exhibits the oxidation peak currents were linearly proportional to their concentration in the range of 0.05-100 ?M for ciprofloxacin, 0.1-100 ?M for ofloxacin, 0.1-40 ?M for norfloxacin and 0.06-100 ?M for gatifloxacin, respectively. This method was also successfully used to detect the concentrations of each drug in pharmaceutical formulations and human serum samples. In addition, this proposed fluoroquinolones sensor exhibited good reproducibility, long-term stability and fast current response. PMID:23498686

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



Long term stability in RHIC  

SciTech Connect

This study of long term stability in RHIC appears to indicate that the dynamic aperture depends on the number of turns the particles are required to survive. The dynamic aperture will decrease as the number of turns is increased. This effect is a non-linear orbit effect, and is present in the absence of synchrotron oscillations or tune ripples, although the presence of synchrotron oscillations or tune ripple may make the effect worse. The effect appears to depend on the choice of {beta}*. It is an appreciable effect for {beta}* = 2 and barely noticeable for {beta}* = 6 in RHIC. Thus, the long term stability effects can be reduced by increasing {beta}*, and accepting the associated loss in luminosity. So far, this study does not include synchrotron oscillations, which may change the results reported here. 2 refs., 16 figs.

Parzen, G.



Issues in long term care.  


Chaplaincy in a long term care facility requires attention to specialized concerns related to the extended length of stay. This article argues the need to (1) retain or restore resident's home church tie; (2) be sensitive to resident/family communications; (3) participate in an interdisciplinary team; (4) understand when to maintain confidentiality and when to speak; (5) know who needs spiritual nourishment. PMID:10312727

Kratz, D G



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.  


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-?RII (T?RII) 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. PMID:21535500

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



Preharvest L-arginine treatment induced postharvest disease resistance to Botrysis cinerea in tomato fruits.  


L-arginine is the precursor of nitric oxide (NO). In order to examine the influence of L-arginine on tomato fruit resistance, preharvest green mature tomato fruits (Solanum lycopersicum cv. No. 4 Zhongshu) were treated with 0.5, 1, and 5 mM L-arginine. The reduced lesion size (in diameter) on fruit caused by Botrytis cinerea, as well as activities of phenylalanine ammonia-lyase (PAL), Chitinase (CHI), ?-1,3-glucanase (GLU), and polyphenoloxidase (PPO), was compared between L-arginine treated fruits and untreated fruits. We found that induced resistance increased and reached the highest level at 3-6 days after treatment. Endogenous NO concentrations were positively correlated with PAL, PPO, CHI, and GLU activities after treatment with Pearson coefficients of 0.71, 0.94, 0.97, and 0.87, respectively. These results indicate that arginine induces disease resistance via its effects on NO biosynthesis and defensive enzyme activity. PMID:21574662

Zheng, Yang; Sheng, Jiping; Zhao, Ruirui; Zhang, Jian; Lv, Shengnan; Liu, Lingyi; Shen, Lin



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

NASA Astrophysics Data System (ADS)

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.

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



NO-dependent and -independent elevation of plasma levels of insulin and glucose in rats by L-arginine.  

PubMed Central

1. L-Arginine elevates plasma insulin in man. Recent in vitro data indicate that this is based on stimulation of endogenous nitric oxide (NO) with subsequent pancreatic release of insulin by L-arginine. L-Arginine also raises plasma glucose. 2. We studied plasma levels of insulin, glucose and NO metabolites, as well as systemic blood pressure, in anaesthetized rats during i.v. infusion of L-arginine (25-200 mg kg-1 min-1) or glucose (55 mg kg-1 min-1), before and after administration of the NO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg kg-1). 3. Before L-NAME, L-arginine elevated plasma insulin from about 15 to 65 ul-1 and glucose from 5.2 to 6.7 mmol l-1. These effects of L-arginine were not dose-related. 4. L-NAME alone had no effect on plasma insulin and glucose levels, but diminished the effects of a low dose (25 mg kg-1 min-1) of L-arginine on plasma insulin by about 40%, and that on plasma glucose by more than 90%. In contrast, the effects of a high dose (200 mg kg-1 min-1) of L-arginine on plasma insulin and glucose levels were not affected by L-NAME. 5. L-NAME elevated systemic blood pressure by about 35 mmHg. L-Arginine (25-100 mg kg-1 min-1) had no effect on systemic blood pressure, either before or after L-NAME. L-Arginine (200 mg kg-1 min-1) lowered systemic blood pressure, both before and after L-NAME. 6. Glucose infusion elevated plasma glucose from about 5.5 to 6.8 mmol l-1, and plasma insulin from about 18 to 26 ul-1. 7. The basal plasma levels of the NO metabolite nitrate (18 +/- 4 mumol l-1) were not affected by L-arginine (200 mg kg-1 min-1). Plasma nitrosohaemoglobin was likewise unaffected by L-arginine (200 mg kg-1 min-1). 8. We conclude that L-arginine separately elevates plasma insulin and glucose levels, both by NO-dependent and -independent mechanisms.

Jun, T; Wennmalm, A



Induction of arginase II by intestinal epithelium promotes the uptake of L-arginine from the lumen of C. parvum infected porcine ileum  

PubMed Central

Objectives To determine the specific transport system activities and expression of transporter genes responsible for uptake of L-arginine from the lumen of normal and C. parvum infected neonatal porcine ileum and the influence of L-arginine catabolic pathways on L-arginine uptake. Methods Intact sheets of ileal mucosa from control and C. parvum infected neonatal piglets were mounted in Ussing chambers and the uptake of 14C-L-arginine was determined under initial rate conditions and in the presence of transport system-selective inhibitors. Epithelial expression of L-arginine transporter genes was quantified by real time RT-PCR. L-arginine catabolic enzyme expression was examined by immunoblotting epithelial lysates for arginase I and II. The role of intracellular catabolism in promoting uptake of L-arginine was determined by pharmacological inhibition of NOS and arginase activities. Results C. parvum infected ileum transported L-arginine at rates equivalent to uninfected epithelium despite profound villous atrophy. This was attributed to enhanced uptake of L-arginine by individual epithelial cells in the infection. There were no differences in L-arginine transport system activities (y+ and B0,+) or level of transporter gene expression (CAT-1, CAT-2A, and ATB0,+) between uninfected and C. parvum infected epithelial cells. However, infected epithelia had induced expression of the L-arginine hydrolytic enzyme arginase II and lower concentrations of L-arginine. Further, transport of L-arginine by the infected epithelium was significantly inhibited by pharmacological blockade of arginase. Conclusions Intracellular catabolism by arginase II, the induction of which has not been previously described for intestinal epithelium, facilitates uptake of L-arginine by infected epithelium using transport systems that do not differ from that of uninfected cells. Induction of arginase II may limit NO synthesis by competing with NOS for utilization of L-arginine or promote use of L-arginine for the synthesis of reparative polyamines.

Gookin, Jody L.; Stauffer, Stephen H.; Coccaro, Maria R.



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


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. PMID:24763427

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



Association of serum arginase I with L-arginine, 3-nitrotyrosine, and exhaled nitric oxide in healthy Japanese workers.  


The associations of serum arginase I with serum L-arginine, serum 3-nitrotyrosine, and fractional exhaled nitric oxide (FENO) were evaluated cross-sectionally in healthy Japanese workers. The serum median (minimum-maximum) levels of arginase I, 3-nitrotyrosine, and FENO in healthy people (n = 130) were 14.6 (0.94-108.1) ng/mL, 81.0 (0.27-298.6) pmol/mg protein, and 14.0 (5.0-110.0) parts per billion, respectively. Significant correlations of arginase I with FENO, L-arginine, 3-nitrotyrosine, and percent predicted forced expiratory volume in 1 s (FEV1 (% predicted)) were observed, and correlations of FENO with immunoglobulin E (IgE), NOx, arginase I, and sex and allergy were also observed. By multiple regression analysis, arginase I showed positive associations with FENO and 3-nitrotyrosine, and a negative association with L-arginine; and FENO showed positive associations with IgE and NO2(-) + NO3(-) (NOx), and a negative association with L-arginine, as well as an association with sex. Moreover, logistic regression analysis showed linear inverse associations of arginase I and 3-nitrotyrosine with L-arginine, and showed linear positive associations of FENO with IgE and NOx. It was concluded that serum arginase I might regulate serum L-arginine and 3-nitrotyrosine via L-arginine, and that IgE or NOx might regulate FENO in a healthy Japanese population. PMID:24060156

Ogino, K; Wang, D H; Kubo, M; Obase, Y; Setiawan, H; Yan, F; Takahashi, H; Zhang, R; Tsukiyama, Y; Yoshida, J; Zou, Y



A Randomized Pilot Study of L-Arginine Infusion in Severe Falciparum Malaria: Preliminary Safety, Efficacy and Pharmacokinetics  

PubMed Central

Background Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed. Methods In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM. Results Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n?=?4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM. Conclusion In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine. Trial Registration NTC00616304

Yeo, Tsin W.; Lampah, Daniel A.; Rooslamiati, Indri; Gitawati, Retno; Tjitra, Emiliana; Kenangalem, Enny; Price, Ric N.; Duffull, Stephen B.; Anstey, Nicholas M.



Synthesis and characterization of nonlinear optical L-arginine semi-oxalate single crystal.  


L-arginine semi-oxalate single crystals have been synthesized by slow evaporation method at room temperature. Single crystal and powder X-ray diffraction analyses has been made to confirm the triclinic structure with non-centrosymmetric space group P1. The presence of functional groups of L-arginine semi-oxalate crystals was identified and confirmed by using the Fourier transform infrared spectroscopy. Molecular structure of the grown crystal was analyzed by 1H NMR and 13C NMR studies. Optical absorption studies carried out in wavelength range from 250 nm to 1200 nm have revealed that the material is completely transparent for the entire wavelength range studied. Thermal characterization using thermogravimetric analysis and differential scanning calorimetry studies show that the crystal is thermally stable up to 146 °C. The presence of second harmonic generation of the grown crystal was tested and its efficiency was determined by using Kurtz and Perry powder technique. PMID:23396007

Vasudevan, P; Gokul Raj, S; Sankar, S



Theoretical studies on vibrational spectra and nonlinear optical property of L-arginine phosphate monohydrate crystal  

NASA Astrophysics Data System (ADS)

Linear and nonlinear optical properties of the organic-inorganic hybrid crystal, L-arginine phosphate monohydrate crystal have been investigated by the first-principles calculation as well as the electronic and vibrational properties. The calculated nonlinear optical coefficients agreed well to the experimental data. The results showed both organic and inorganic structural building blocks contribute to the large nonlinear optical activities of this crystal and the significant contribution of the intermolecular hydrogen bonds. The absorption-edges on both IR and UV sides of LAP crystal have been estimated and the structure-property relationship has been discussed. The study is helpful to the further development of L-arginine phosphate monohydrate crystal analogs with improved nonlinear optical properties.

Wu, Kechen; Liu, Caiping; Mang, Chaoyong



Rapid, one-pot synthesis of highly-soluble carbon nanotubes functionalized by L-arginine  

NASA Astrophysics Data System (ADS)

Functionalization of carbon nanotubes (CNTs) is a necessary step to exploit their valuable properties. Due to having several steps and especially acid treatment, most of current methods of functionalization result in irrecoverable defects on CNTs structure. Here, multiwalled carbon nanotubes (MWCNTs) were functionalized with L-arginine in a simple, one-pot and rapid microwave-assisted technique without any acid treatment step. The CNT functionalities were analyzed with infrared spectroscopy, thermogravimetric analysis, Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy. The results confirmed the covalent functionalization of L-arginine with very low defects on CNTs. Also it is found that increase of input powers of microwave in the range 500-900 W, monotonically increase the degree of functionalization. The maximum dispersibility of MWCNT was found ˜1.03 mg/mL corresponding to 900 W irradiation. Accounting considerable low treatment time, the method may be applied for large-scale solubilization of MWCNTs in an industrial scale.

Ghiadi, Behnam; Baniadam, Majid; Maghrebi, Morteza; Amiri, Ahmad



Synthesis and characterization of nonlinear optical L-arginine semi-oxalate single crystal  

NASA Astrophysics Data System (ADS)

L-arginine semi-oxalate single crystals have been synthesized by slow evaporation method at room temperature. Single crystal and powder X-ray diffraction analyses has been made to confirm the triclinic structure with non-centrosymmetric space group P1. The presence of functional groups of L-arginine semi-oxalate crystals was identified and confirmed by using the Fourier transform infrared spectroscopy. Molecular structure of the grown crystal was analyzed by 1H NMR and 13C NMR studies. Optical absorption studies carried out in wavelength range from 250 nm to 1200 nm have revealed that the material is completely transparent for the entire wavelength range studied. Thermal characterization using thermogravimetric analysis and differential scanning calorimetry studies show that the crystal is thermally stable up to 146 °C. The presence of second harmonic generation of the grown crystal was tested and its efficiency was determined by using Kurtz and Perry powder technique.

Vasudevan, P.; Gokul Raj, S.; Sankar, S.



Long-Term Care Ombudsman Program  


... shortly. Unable to Share This Page Long-Term Care Ombudsman Program (OAA, Title VII, Chapter 2, Sections ... Services Provided to Persons Living in Long-Term Care Facilities Program data for FY 2011 indicate that ...


Growth of nonlinear optical material: L-arginine hydrochloride and its characterisation  

NASA Astrophysics Data System (ADS)

L-arginine hydrochloride crystals have been grown using water and ethanol+water mixture as solvent. Growth of the anhydrous form of LAHCl has also been carried out. The grown crystals were subjected to powder X-ray diffraction studies. FTIR studies have been carried out to identify the functional groups present in the crystal. TGA and optical transmission studies have also been made on the grown crystals. The grown crystals were subjected to etching and microhardness studies.

Meera, K.; Muralidharan, R.; Dhanasekaran, R.; Manyum, Prapun; Ramasamy, P.



The role of antioxidants in models of inflammation: Emphasis on l -arginine and arachidonic acid metabolism  

Microsoft Academic Search

Inflammatory processes are made up of a multitude of complex cascades. Under physiological conditions these processes aid\\u000a in tissue repair. However, under pathophysiological environments, such as wound healing and hypoxia-ischaemia (HI), inflammatory\\u000a mediators become imbalanced, resulting in tissue destruction. This review addresses the changes in reactive oxygen species\\u000a (ROS), l-arginine and arachidonic acid metabolism in wound healing and HI and

M. Kapoor; A. N. Clarkson; B. A. Sutherland; I. Appleton



ynthesis and Characterization of Pure and Doped L- Arginine Maleate Single Crystals  

NASA Astrophysics Data System (ADS)

Pure and Doped L- Arginine Maleate (LArM) a nonlinear optical material has been successfully grown from slow evaporation method. FTIR analysis was used to confirm the presence of various functional groups in the grown crystals. Kurtz powder SHG measurements confirm the NLO property of the grown crystal. X- Ray powder diffraction studies have been carried out in order to calculate the lattice parameter values.

Karunanithi, U.



Studies on growth defects and mechanical properties of nonlinear optical crystal: L-arginine hydrofluoride  

NASA Astrophysics Data System (ADS)

Chemical etching technique has been used for the first time to reveal dislocation structure of the cleavage plane of L-arginine hydrofluoride monohydrate (LAHF). Selective behaviour of the etchants for revealing macrosteps and cooperating spirals has been demonstrated. Presence of growth spirals on (1 0 0) face indicates that growth of this face is governed by screw dislocation mechanism. Microhardness measurement reveals that LAHF is harder than LAP.

Pal, Tanusri; Kar, Tanusree



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


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. PMID:20718864

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



Growth morphology of {1 0 1} surfaces of L-arginine trifluoroacetate crystals investigated by AFM  

NASA Astrophysics Data System (ADS)

Surface morphology of {1 0 1} surfaces of L-arginine trifluoroacetate (LATF) crystals have been investigated by atomic force microscopy (AFM). The dominant growth mechanism of the LATF crystals is the formation and expansion of dislocation spirals. Rectangular dislocation growth hillocks oriented with their longer sides in the [0 1 0] direction, which indicates the fast growth along this direction. Apart from that, typical step morphologies are presented and discussed on the basis of the observations.

Liu, X. J.; Wang, Z. Y.; Yu, G. W.; Sun, Z. H.; Zhang, G. H.; Wang, X. Q.; Zhu, L. Y.; Yu, G.; Xu, D.



Thermal, mechanical, electrical, linear and nonlinear optical properties of L-arginine dihydrofluoride single crystal  

NASA Astrophysics Data System (ADS)

L-arginine dihydrofluoride of dimensions upto 15×10×9 mm 3 was successfully grown by slow evaporation technique from aqueous solution. The crystal was characterized by X-ray diffractometry, Elemental analysis, FT-IR, UV-Vis-NIR spectroscopy, thermal and microhardness studies. The dielectric constant and dielectric loss of the crystal were studied as function of frequency. Photoconductivity studies were also carried out on the sample. Kurtz powder SHG measurement confirms the NLO property of the grown crystals.

Sankar, D.; Menon, Vinay Raj; Sagayaraj, P.; Madhavan, J.



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

SciTech Connect

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

Cheng Wei [Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan); Oike, Masahiro [Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan)]. E-mail:; Hirakawa, Masakazu [Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan); Ohnaka, Keizo [Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan); Koyama, Tetsuya [Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan); Ito, Yushi [Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-82 (Japan)



Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization  

Microsoft Academic Search

.   Nitric oxide (NO) is a recently discovered mediator produced by mammalian cells. It plays a key role in neurotransmission,\\u000a control of blood pressure, and cellular defense mechanisms. Nitric oxide synthases (NOSs) catalyze the oxidation of L-arginine\\u000a to NO and L-citrulline. NOSs are unique enzymes in that they possess on the same polypeptidic chain a reductase domain and\\u000a an oxygenase

J. L. Boucher; C. Moali; J. P. Tenu



Influence of hydrogen bonds on charge distribution and conformation of L-arginine  

NASA Astrophysics Data System (ADS)

The molecular recognition of adenosine-5'-triphosphate (ATP) with L-arginine (Arg) through hydrogen bonding interactions has been found using 1H NMR, H-H NOESY, acidity titration and fluorescence spectra techniques. The interactions could influence charge distribution in Arg and induce Arg conformational variation. It is realized that Arg conformation change from a partly folded state to an extended state through the rotation of C sbnd C single bonds of Arg side chain during the molecular recognition process.

Xian, Liang; Liu, Shuhua; Ma, Yanqing; Lu, Gongxuan



Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate  

Microsoft Academic Search

Previous studies have shown that murine macrophages immunostimulated with interferon ..gamma.. and Escherichia coli lipopolysaccharide synthesize NOâ⁻, NOâ⁻, and citrulline from L-arginine by oxidation of one of the two chemically equivalent guanido nitrogens. The enzymatic activity for this very unusual reaction was found in the 100,000g supernatant isolated from activated RAW 264.7 cells and was totally absent in unstimulated cells.

Michael A. Marletta; Poksyn S. Yoon; Radha Iyengar; Cynthia D. Leaf; John S. Wishnok



Crystal growth of high quality nonlinear optical crystals of L-arginine trifluoroacetate  

NASA Astrophysics Data System (ADS)

Grow of good optical quality single crystals of L-arginine trifluoroacetate (LATF), a new semiorganic nonlinear optical (NLO) material is reported. Bulk crystals have been successfully grown from solution by the temperature lowering method. Growth rate and effects of seed orientation on morphologies of LATF crystals were studied. The crystals were characterized by density measurement, optical absorption spectrum, differential scanning calorimetry (DSC) and microhardness studies.

Liu, Xiaojing; Wang, Zeyan; Zhang, Guanghui; Wang, Xinqiang; Duan, Aidong; Sun, Zhihua; Zhu, Luyi; Xu, Dong



Alterations in l -arginine and inflammatory markers in type 2 diabetic patients with and without microalbuminuria  

Microsoft Academic Search

Low-grade inflammation is closely involved in the pathogenesis of type 2 diabetes and associated micro- and macrovascular\\u000a complications. The nitric oxide (NO) precursor l-arginine, is relevant to diverse pathological conditions including type 2 diabetes and its complications. High sensitive-CRP\\u000a (hs-CRP), neopterin and arginine levels were measured in 46 normoalbuminuric, 45 microalbuminuric type 2 diabetics and in\\u000a 32 healthy controls in

Necla Bar??; Mehmet Erdo?an; Ebru Sezer; Füsun Sayg?l?; A. Mert Özgönül; Nevbahar Turgan; Biltan Ersöz



Ascorbic acid or l-arginine improves cutaneous microvascular function in chronic kidney disease  

PubMed Central

We sought to determine whether oxidative stress or a relative deficit of l-arginine plays a role in reducing cutaneous vasodilation in response to local heating in chronic kidney disease (CKD). Eight patients with stage 3–4 CKD and eight age- and sex-matched healthy control (HC) subjects were instrumented with four microdialysis (MD) fibers for the local delivery of 1) Ringers solution (R), 2) 20 mM ascorbic acid (AA), 3) 10 mM l-arginine (l-Arg), and 4) 10 mM NG-nitro-l-arginine methyl ester (l-NAME). Red blood cell (RBC) flux was measured via laser Doppler flowmetry. A standardized nonpainful local heating protocol (42°C) was used. Cutaneous vascular conductance (CVC) was calculated as RBC flux/MAP and all data were expressed as a percentage of the maximum CVC at each site (28 mM sodium nitroprusside, Tloc = 43°C). The plateau %CVCmax was attenuated in CKD (CKD: 76 ± 4 vs. HC: 91 ± 2%CVCmax; P < 0.05) and the NO contribution to the plateau was lower in CKD (CKD: 39 ± 7, HC: 54 ± 5; P < 0.05). The plateau %CVCmax in the CKD group was significantly greater at the AA and l-Arg sites compared with R (AA: 89 ± 2; l-Arg: 90 ± 1; R: 76 ± 4; P < 0.05) and did not differ from HC. Initial peak %CVCmax was also significantly attenuated at the R and l-Arg sites in CKD (P < 0.05) but did not differ at the AA site. These results suggest that cutaneous microvascular function is impaired in stage 3–4 CKD and that oxidative stress and a deficit of l-arginine play a role in this impairment.

DuPont, Jennifer J.; Farquhar, William B.; Townsend, Raymond R.



Dietary L-Arginine Normalizes Endothelin-Induced Vascular Contractions in Cholesterol-Fed Rabbits  

Microsoft Academic Search

Summary: The endothelium regulates vascular function by re- leasing the vasodilator autacoid nitric oxide (NO) and the vaso- constrictor peptide endothelin-I (ET-I). Impaired activity of NO as well as excessive activity of ET-I have been demon- strated in hypercholesterolemia and atherosclerosis. Because dietary L-arginine can restore NO function and improve abnor- mal endothelium-dependent relaxation in hypercholesterolemic rabbits, we examined the

Laddawal Phivthong-ngam; Stefanie M. Bode-Boger; Rainer H. Boger; Michael Bohme; Ralf P. Brandes; Jiirgen C. Frolich


Myocardial Contractile Effects of l-Arginine in the Human Allograft  

Microsoft Academic Search

Objectives. In the present study, we investigated, in transplant recipients, whether l-arginine (l-arg) potentiates the myocardial contractile effects of receptor-mediated coronary endothelial stimulation. Moreover, because inducible nitric oxide synthase (iNOS) is frequently expressed in transplanted myocardium, we also performed intracoronary infusion of l-arg in the absence of receptor-mediated coronary endothelial stimulation to investigate whether similar left ventricular (LV) contractile effects

Walter J. Paulus; Stefanie Kästner; Marc Vanderheyden; Ajay M. Shah; Helmut Drexler



Pricing and hedging long-term options  

Microsoft Academic Search

Do long-term and short-term options contain differential information? If so, can long-term options better differentiate among alternative models? To answer these questions, we first demonstrate analytically that differences among alternative models usually may not surface when applied to short-term options, but do so when applied to long-term contracts. Using S&P 500 options and LEAPS, we find that short- and long-term

Gurdip Bakshi; Charles Cao; Zhiwu Chen



Component crystallization and physical collapse during freeze-drying of L-arginine-citric acid mixtures.  


Component crystallization and physical collapse during freeze-drying of aqueous solutions containing protein-stabilizing L-arginine and citric acid mixtures were studied. Freeze-drying microscopy (FDM) and thermal analysis of the solute-mixture frozen solutions showed collapse onset at temperatures (T(c)) approximately 10°C higher than their T(g)'s (glass transition temperatures of the maximally freeze-concentrated solute phase). Experimental freeze-drying of these solutions at a low chamber pressure showed the occurrence of physical collapse at shelf temperatures close to or slightly higher than the T(c). Slower ice sublimation at higher chamber pressures induced the physical collapse from lower shelf temperatures. The large effect of chamber pressures on the collapse-inducing shelf temperatures confirmed significance of the sublimation-related heat loss on the sublimation interface temperature during the primary drying. Drying of the single-solute L-arginine solution resulted in cake-structure solids composed of its anhydrous crystal. Thermal and powder X-ray diffraction (PXRD) analysis suggested slow crystal nucleation of L-arginine dihydrate in the frozen solutions. Characterization of the frozen solutions and freeze-dried solids should enable rational formulation design and process control of amino acid-containing lyophilized pharmaceuticals. PMID:22976327

Yamaki, Takuya; Ohdate, Ryohei; Nakadai, Eriko; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Moriyama, Hiroshi; Izutsu, Ken-ichi; Yomota, Chikako; Okuda, Haruhiro; Kawanishi, Toru



L-Arginine/NO Pathway Is Altered in Children with Haemolytic-Uraemic Syndrome (HUS)  

PubMed Central

The haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal failure in childhood. We investigated L-arginine/NO pathway in 12 children with typical HUS and 12 age-matched healthy control subjects. Nitrite and nitrate, the major NO metabolites in plasma and urine, asymmetric dimethylarginine (ADMA) in plasma and urine, and dimethylamine (DMA) in urine were determined by GC-MS and GC-MS/MS techniques. Urinary measurements were corrected for creatinine excretion. Plasma nitrate was significantly higher in HUS patients compared to healthy controls (P = 0.021), whereas urine nitrate was borderline lower in HUS patients compared to healthy controls (P = 0.24). ADMA plasma concentrations were insignificantly lower, but urine ADMA levels were significantly lower in the HUS patients (P = 0.019). Urinary DMA was not significantly elevated. In HUS patients, nitrate (R = 0.91) but not nitrite, L-arginine, or ADMA concentrations in plasma correlated with free haemoglobin concentration. Our results suggest that both NO production and ADMA synthesis are decreased in children with typical HUS. We hypothesize that in the circulation of children with HUS a vicious circle between the L-arginine/NO pathway and free haemoglobin-mediated oxidative stress exists. Disruption of this vicious circle by drugs that release NO and/or sulphydryl groups-containing drugs may offer new therapeutic options in HUS.

Kanzelmeyer, Nele Kirsten; Pape, Lars; Chobanyan-Jurgens, Kristine; Tsikas, Dimitrios; Fuchs, Anne-Jule; Vaske, Bernhard; Das, Anibh Martin; Haubitz, Marion; Jordan, Jens; Lucke, Thomas



Long-Term Planning in Higher Education.  

ERIC Educational Resources Information Center

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…

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


Long Term Surface Salinity Measurements  

NASA Technical Reports Server (NTRS)

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.

Schmitt, Raymond W.; Brown, Neil L.



Long-term competence restoration.  


While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed. PMID:24618523

Morris, Douglas R; DeYoung, Nathaniel J



Long-term stellar variability  

NASA Astrophysics Data System (ADS)

Stars with significant subsurface convection zones develop magnetic loop structures that, arising from the surface upward to the external atmospheres, cause flux variability detectable throughout the whole electromagnetic spectrum. In fact, diagnostics of magnetic activity are in radio wavelengths, where gyrosincrotron radiation arises from the quiescent and flaring corona; in the optical region, where important signatures are the Balmer lines, the Ca ii IRT and H&K lines; in the UV and X ray domains, the latter mainly due to coronal thermal plasma. The zoo of different magnetic features observed for the Sun - spots, faculae, flares, CMEs - are characterized by different temporal evolution and energetics, both in quantity and quality. As a consequence, the time scale of variability, the amount of involved energy and the quality of the involved photons are used as fingerprints in interpreting the observed stellar variability in the framework of the solar-stellar analogy. Here I review main results from long-term multiwavelength observations of cool star atmospheres, with emphasis to similarities and differences with the solar case.

Pagano, Isabella



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

NASA Astrophysics Data System (ADS)

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 administration allows maintaining NO concentration in m.soleus at the level of cage control group, prevents from dystrophin layer destruction, decreases the atrogin mRNA concentration in the muscle and atrophy level under gravitational unloading.

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



Hormonal response to L-arginine supplementation in physically active individuals  

PubMed Central

Background Nutritional supplements based on the amino acid L-arginine have been hypothesized to improve exercise performance by increasing levels of insulin and growth hormone (GH). Changes of these parameters in response to L-arginine supplementation may clarify the mechanisms underlying its putative physiological effects on physical performance. Objective The aim of the study was to evaluate the effect of L-arginine supplementation on serum insulin, GH, Growth Factor Insulin-like (IGF-1), and cortisol in response to exercise. Exercise performance was also evaluated. Design Fifteen trained runners were divided into groups supplemented with 6 g of L-arginine (ARG) or placebo (PLA). Blood samples were collected before supplementation (T0), immediately after the first exercise session (T1), after the second exercise session (T2), and after 20 min of rest (T3). The exercise consisted of two bouts of 5 km time-trial running test. Results There was a significant increase in serum GH (T0: 3.28±0.95 vs. 3.21±0.5 ng/mL; T1: 4.35±0.23 vs. 4.17±0.13 ng/mL; T2: 4.22±0.25 vs. 4.17±0.09 ng/mL; T3: 4.14±0.29 vs. 4.13±0.18 ng/mL) and cortisol (T0: 198.71±53.77 vs. 207.57±69.51 nmol/L; T1: 458.16±116.12 vs. 433.26±101.77 nmol/L; T2: 454.61±125.21 vs. 431.88±74.82 nmol/L; T3: 311.14±102.91 vs. 362.26±110.42 nmol/L) after T1, T2, and T3, with no significant difference between the ARG and PLA groups, respectively. There was also no significant difference observed in the variables of IGF-1, insulin, and total running time between the ARG and PLA groups. Conclusions The supplementation of L-arginine did not appear to stimulate the production of insulin, GH, and IGF-1 and, thus, provided no benefit in hormonal response or exercise performance in trained runners.

da Silva, Davi Vieira Teixeira; Conte-Junior, Carlos Adam; Paschoalin, Vania Margaret Flosi; Alvares, Thiago da Silveira



One-Pot Green Synthesis and Bioapplication of l-Arginine-Capped Superparamagnetic Fe3O4 Nanoparticles  

NASA Astrophysics Data System (ADS)

Water-soluble l-arginine-capped Fe3O4 nanoparticles were synthesized using a one-pot and green method. Nontoxic, renewable and inexpensive reagents including FeCl3, l-arginine, glycerol and water were chosen as raw materials. Fe3O4 nanoparticles show different dispersive states in acidic and alkaline solutions for the two distinct forms of surface binding l-arginine. Powder X-ray diffraction and X-ray photoelectron spectroscopy were used to identify the structure of Fe3O4 nanocrystals. The products behave like superparamagnetism at room temperature with saturation magnetization of 49.9 emu g-1 and negligible remanence or coercivity. In the presence of 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride, the anti-chloramphenicol monoclonal antibodies were connected to the l-arginine-capped magnetite nanoparticles. The as-prepared conjugates could be used in immunomagnetic assay.

Lai, Yongchao; Yin, Weiwei; Liu, Jinting; Xi, Rimo; Zhan, Jinhua



Early malnutrition, but not age, modulates in the rat the l-Arginine facilitating effect on cortical spreading depression  

Microsoft Academic Search

Nutritional factors acting during brain development can permanently alter brain electrophysiology. l-Arginine is the precursor of nitric oxide synthesis, which can modulate brain function. Here we investigated the effect of early-in-life administration (during postnatal days 7–28) of l-Arginine (300mg\\/(kgday)) on cortical spreading depression (CSD), recorded in well-nourished and malnourished (large litters technique) rats aged 30–40 days (young) and 90–110 days

Marília Ferreira Frazão; Luciana Maria Silva de Seixas Maia; Rubem Carlos Araújo Guedes



L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of ischemic acute renal failure in rats  

Microsoft Academic Search

L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of ischemic acute renal failure in rats.BackgroundIn ischemic acute renal failure (ARF), nitric oxide–dependent regulation of renal hemodynamics and glomerular function is disturbed. Previous studies indicate that the nitric oxide precursor L-arginine (L-Arg) has beneficial effects on renal function. Here we further analyzed the impact of L-Arg on functional and

Reinhard Schneider; Ulrike Raff; Nicole Vornberger; Monika Schmidt; Ralf Freund; Mark Reber; Lothar Schramm; Stepan Gambaryan; Christoph Wanner; Harald H. H. W. Schmidt; Jan Galle



The L-Arginine: Nitric Oxide Pathway Is the Major Source of Plasma Nitrite in Fasted Humans  

Microsoft Academic Search

15N guanidino-labelled L-arginine was infused into fasted human volunteers giving, at equilibrium, a stable 1:10 ratio of 15N to 14N arginine in the plasma. Separate GC-MS assays were used to compare the degree of enrichment of plasma arginine, nitrite and nitrate and thus define the quantitative relationship between the L-arginine:nitric oxide (NO) pathway and the formation of these oxides of

P. M. Rhodes; A. M. Leone; P. L. Francis; A. D. Struthers; S. Moncada



Cardiovascular and neurohormonal responses to i. v. l-arginine in two groups with primary autonomic failure  

Microsoft Academic Search

Nitric oxide (NO) is synthesised from the amino-acid l-arginine by the enzyme nitric oxide synthetase (NOS) and modulates\\u000a a wide variety of neural, cardiovascular and hormonal processes. Cardiovascular autonomic dysfunction and impaired neurohormonal\\u000a secretion characterise patients with primary chronic autonomic failure (AF). To investigate the role of NO, we studied the\\u000a cardiovascular and neurohormonal effects of intravenous (i. v.) l-arginine

J. Kimber; L. Watson; C. J. Mathias



Early malnutrition, but not age, modulates in the rat the L-Arginine facilitating effect on cortical spreading depression.  


Nutritional factors acting during brain development can permanently alter brain electrophysiology. L-Arginine is the precursor of nitric oxide synthesis, which can modulate brain function. Here we investigated the effect of early-in-life administration (during postnatal days 7-28) of L-Arginine (300 mg/(kg day)) on cortical spreading depression (CSD), recorded in well-nourished and malnourished (large litters technique) rats aged 30-40 days (young) and 90-110 days (adult). Compared to water-treated controls, well-nourished L-Arginine-treated rats, but not the malnourished ones, displayed higher CSD velocities (P<0.05) at both ages. The mean+/-S.D. CSD velocities (in mm/min) were: for water- and L-Arginine well-nourished rats, 3.78+/-0.23 and 4.36+/-0.19 (young groups), and 3.28+/-0.16 and 4.09+/-0.30 (adult); for the same conditions in the malnourished rats, 4.22+/-0.09 and 4.27+/-0.21 (young), and 4.11+/-0.18 and 4.21+/-0.33 (adult). L-Arginine treatment did not affect body and brain weights. It is concluded that early L-Arginine treatment long lastingly increased brain CSD-susceptibility and this effect is abolished by early malnutrition. PMID:18838105

Frazão, Marília Ferreira; Silva de Seixas Maia, Luciana Maria; Guedes, Rubem Carlos Araújo



The effect of L-arginine and L-NAME on myocardial capillary density in normal rats  

PubMed Central

Background: This study evaluated the effect of L-arginine (Nitric Oxide (NO) precursor) and L-NG-Nitroarginine Methyl Ester (L-NAME) (NO synthase inhibitor) on myocardial capillary density in normal rats. Materials and Methods: Eighteen male rats were divided into three groups: Group 1: Received L-NAME (10 mg/kg/day; ip), Group 2: Received L-arginine (50 mg/kg/day; ip), and Group 3 (control) received normal saline. After 3 weeks, blood samples were taken and myocardial capillary density was evaluated using immunohistochemistry method. Results: Serum NO concentration in control group was 6.45 ± 0.44 ?mol/lit. Treatment of animals with L-arginine increased serum NO concentration (7.90 ± 0.75 vs. 6.45 ± 0.44 ?mol/lit, respectively) and L-NAME decreased (4.86 ± 0.40 vs. 6.45 ± 0.44 ?mol/lit, respectively) compare to control group. L-arginine significantly increased serum vascular endothelial growth factor (VEGF) concentration (353.01 ± 7.03 vs. 100.5 ± 6.61 pg/ml; P < 0.05), however, did not change myocardial capillary density. Conclusion: Although L-arginine alters some serum angiogenic factors, either L-arginine or L-NAME could not improve myocardial capillary density in normal rats.

Khazaei, Majid; Moshayedi, Muhammad Amin; Jervekani, Massoud Teimouri; Aghili, Shahrzad; Montazer, Saeed; Dastjerdi, Roshanak Mehdipour; Hashemzehi, Fazlolah; Jazi, Hourossadat Hashemi



Long-term solar-terrestrial observations  

NASA Technical Reports Server (NTRS)

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.



Financing Reform for Long-Term Care  

Microsoft Academic Search

The way the nation provides for the financing and delivery of long-term care is badly in need of reform. The principal options for change are private insurance, altering Medicaid, and 110 FROM NURSJNG HOMES TO HOME CARE public long-term care insurance. This article uses the Brookings-ICE Long-Term Care Financing Model to evaluate each of these options in terms of affordability,

Joshua M. Wiener



The role of the L-arginine-nitric oxide pathway in preeclampsia.  


Preeclampsia (PE) is a major cause of maternal and perinatal mortality, especially in developing countries. Its etiology involves multiple factors, but no specific cause has been identified. Evidence suggests that clinical manifestations are caused by endothelial dysfunction. Nitric oxide (NO), which is synthesized from L-arginine in endothelial cells by the endothelial nitric oxide synthase (eNOS), provides a tonic dilator tone and regulates the adhesion of white blood cells and platelet aggregation. Alterations in the L-arginine-NO pathway have been associated with the development of PE. Various studies, reporting decreased, elevated or unchanged levels of nitrite (NO(2)) and nitrate (NO(3)), two end products of NO metabolism, have been published. Our group contributed to those contradictory reports describing cases of PE with both elevated and decreased levels of NO(2) and NO(3). Apparently, diminished levels of NO could be related to deficiencies in the ingestion of dietary calcium associated to low levels of plasma ionic calcium, which is crucial to the eNOS' activity. Also, low levels of NO could be associated with the presence of eNOS polymorphisms or the presence of increased levels of ADMA, the endogenous inhibitor of NO. High levels of NO associated to low levels of cGMP suggest a decreased bioactivity of NO, which is probably related to an increased degradation of NO caused by a high production of superoxide in states of infection and inflammation. The present article analyses and reviews the reported paradoxical roles of the L-arginine-NO pathway in PE and gives a possible explanation for these results. PMID:19124426

López-Jaramillo, Patricio; Arenas, William D; García, Ronald G; Rincon, Melvin Y; López, Marcos



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

PubMed Central

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.

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



Long-term correlations in earth sciences  

NASA Astrophysics Data System (ADS)

In this article we review the occurrence and consequences of long-term memory in geophysical records like climate and seismic records, and describe similarities with financial data sets. We review several methods to detect linear and nonlinear long-term correlations, also in the presence of external trends, and show how external trends can be detected in data with long-term memory. We show as well that long-term correlations lead to a natural clustering of extreme events and discuss the implications for several geophysical data sets.

Bunde, Armin; Lennartz, Sabine



Studies on surface micromorphology and growth mechanism of nonlinear optical crystal: L-arginine hydrochlorobromo monohydrate  

NASA Astrophysics Data System (ADS)

Chemical etching technique has been used for the first time to reveal dislocation structure of the L-arginine hydrochlorobromo monohydrate, C 6H 14N 4O 2HClBr.H 2O crystal on the polished {1 0 0}, {0 1 0} and {0 0 1} faces. Fast dissolving etchants could produce etch pits only on the 'F' faces but they have no effect on the 'S' face. Selective behaviour of the etchants for revealing inclined dislocations and cooperating spirals has been demonstrated. Presence of growth spirals on (1 0 0) face indicates that growth of this face is governed by screw dislocation mechanism.

Pal, Tanusri; Kar, Tanusree



Growth and Surface Morphology of {101} Cleavage Planes of L-Arginine Trifluoroacetate Crystals  

NASA Astrophysics Data System (ADS)

Single crystals of nonlinear optical material, L-arginine trifluoroacetate (abbreviated as LATF), were grown from an aqueous solution by the low temperature solution growth method. The cell parameters of the grown crystal were determined by the X-ray powder diffraction analysis. Atomic force microscopy (AFM) was used to investigate the surface morphology of {101} cleavage faces of LATF. Straight steps and two-dimensional nuclei were observed. Liquid inclusions and impurities as defects for revealing macrosteps were demonstrated. The molecular structure and crystal structure correlative with surface morphology were discussed.

Sun, Z. H.; Xu, D.; Yu, G. W.; Zhang, G. H.; Wang, X. Q.; Liu, X. J.; Zhu, L. Y.; Yu, G.; Fan, H. L.


Growth and characterization of NLO based L-arginine maleate dihydrate single crystal  

NASA Astrophysics Data System (ADS)

Single crystals of L-arginine maleate dihydrate (LAMD) were successfully grown from aqueous solution by solvent evaporation technique. As-grown crystals were analyzed by different instrumentation techniques such as X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectra and UV-vis near infrared (NIR) transmittance spectra. Thermal behavior has been studied with TGA/DTA analyses. The optical second harmonic generation (SHG) conversion efficiency of LAMD was determined using Kurtz powder technique and found to be 1.5 times that of KDP.

Baraniraj, T.; Philominathan, P.



AFM investigation of the {101} surface morphology of L-arginine trifluoroacetate (LATF) crystals  

NASA Astrophysics Data System (ADS)

The {101} surface of L-arginine trifluoroacetate (LATF) crystals has been investigated by ex situ atomic force microscopy (AFM). The main step sources were observed in the form of growth spirals. The growth spirals are rounded and highly anisotropic. Microcrystals transferred from aggregates deposit at the step-edged on the facets. It is suggested that the microcrystals may lead to the formation of macrodefects during growth. Etching experiments reveal circular hollow cores, indicative of both screw dislocation growth, and negative crystals generated by further crystallization in the entrapped liquid inclusions are investigated.

Liu, X. J.; Wang, Z. Y.; Duan, A. D.; Yu, G.; Zhang, G. H.; Yu, G. W.; Wang, X. Q.; Sun, Z. H.; Xu, D.



Temperature-insensitive phase matching for second-harmonic generation in deuterated l -arginine phosphate  

SciTech Connect

We present measurements of the thermal behavior of the second-harmonic generation (SHG) phase-matching loci of deuterated {ital l}-arginine phosphate (dLAP) at a fundamental wavelength of 1.064 {mu}m. These results clearly indicate the existence of temperature-insensitive phase-matching directions that possess large nonlinear couplings. To the best of our knowledge, this property of temperature-insensitive SHG phase-matching directions is unique to dLAP. Such behavior can greatly decrease thermal contributions to phase mismatch in high-average-power harmonic conversion.

Barker, C.E.; Eimerl, D.; Velsko, S.P. (Lawrence Livermore National Laboratory, University of California, M.S. L-490, P. O. Box 808, Livermore, California 94550 (United States))



Different effects of L-arginine on morphine tolerance in sham and ovariectomized female mice*  

PubMed Central

Objective: The roles of gonadal hormones and nitric oxide (NO) on the analgesic effects of morphine, tolerance to morphine, and their interactions have been widely investigated. In the present study, the effect of L-arginine (an NO precursor) on morphine tolerance in sham and ovariectomized (OVX) female mice was investigated. Methods: Forty mice were divided into sham and OVX groups. On the first day, a hot plate test ((55±0.2) °C; cut-off 30 s) was carried out as a base record 15 min before injection of morphine (10 mg/kg, subcutaneously (s.c.)) and was repeated every 15 min after injection. The sham group was then divided into two subgroups: sham-tolerance-L-arginine (Sham-Tol-LA) and sham-tolerance-saline (Sham-Tol-Sal) which received either L-arginine 50 mg/kg (intraperitoneally (i.p.)) or saline 10 ml/kg (i.p.), respectively, three times in a day for three consecutive days. Morphine tolerance was induced in animals by injecting 30 mg/kg morphine (s.c.) three times/day for three days. This treatment was also used for OVX subgroups. On the fifth day, the hot plate test was repeated. The analgesic effect of morphine was calculated as the maximal percent effect (MPE). The results were compared using repeated measure analysis of variance (ANOVA). Results: There was no significant difference in MPE between the OVX and sham groups. The MPEs in both the Sham-Tol-Sal and OVX-Tol-Sal groups were lower than those in both the sham and OVX groups (P<0.01). The MPE in the OVX-Tol-Sal group was greater than that in the Sham-Tol-Sal group (P<0.01). The MPE in the Sham-Tol-LA group was higher than that in the Sham-Tol-Sal group (P<0.01). However, there was no significant difference between the Sham-Tol-LA and sham groups or between the OVX-Tol-LA and OVX-Tol-Sal groups. Conclusions: The results of the present study showed that repeated administration of morphine causes tolerance to the analgesic effect of morphine. L-Arginine could prevent tolerance to morphine but its effect was different in the presence of ovarian hormones.

Karami, Reza; Hosseini, Mahmoud; Khodabandehloo, Fatimeh; Khatami, Leila; Taiarani, Zahra



An Association between l-Arginine/Asymmetric Dimethyl Arginine Balance, Obesity, and the Age of Asthma Onset Phenotype  

PubMed Central

Rationale: Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (FeNO). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to l-arginine, which can lead to greater nitric oxide synthase uncoupling. Objectives: To compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function. Methods: Cross-sectional study of participants from the Severe Asthma Research Program, across early- (<12 yr) and late- (>12 yr) onset asthma phenotypes. Measurements and Main Results: Subjects with late-onset asthma had a higher median plasma ADMA level (0.48 ?M, [interquartile range (IQR), 0.35–0.7] compared with early onset, 0.37 ?M [IQR, 0.29–0.59], P = 0.01) and lower median plasma l-arginine (late onset, 52.3 [IQR, 43–61] compared with early onset, 51 ?M [IQR 39–66]; P = 0.02). The log of plasma l-arginine/ADMA was inversely correlated with BMI in the late- (r = ?0.4, P = 0.0006) in contrast to the early-onset phenotype (r = ?0.2, P = 0.07). Although FeNO was inversely associated with BMI in the late-onset phenotype (P = 0.02), the relationship was lost after adjusting for l-arginine/ADMA. Also in this phenotype, a reduced l-arginine/ADMA was associated with less IgE, increased respiratory symptoms, lower lung volumes, and worse asthma quality of life. Conclusions: In late-onset asthma phenotype, plasma ratios of l-arginine to ADMA may explain the inverse relationship of BMI to FeNO. In addition, these lower l-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype.

Comhair, Suzy A. A.; Hazen, Stanley L.; Powers, Robert W.; Khatri, Sumita S.; Bleecker, Eugene R.; Busse, William W.; Calhoun, William J.; Castro, Mario; Fitzpatrick, Anne M.; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar N.; Moore, Wendy C.; Peters, Stephen P.; Teague, W. Gerald; Chung, Kian Fan; Erzurum, Serpil C.; Wenzel, Sally E.



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


Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea-cycle disorder, and leads to deficiency of both ureagenesis and NO production. Subjects with ASA have been reported to develop long-term complications such as hypertension and neurocognitive deficits despite early initiation of therapy and the absence of documented hyperammonemia. In order to distinguish the relative contributions of the hepatic urea-cycle defect from those of the NO deficiency to the phenotype, we performed liver-directed gene therapy in a mouse model of ASA. Whereas the gene therapy corrected the ureagenesis defect, the systemic hypertension in mice could be corrected by treatment with an exogenous NO source. In an ASA subject with severe hypertension refractory to antihypertensive medications, monotherapy with NO supplements resulted in the long-term control of hypertension and a decrease in cardiac hypertrophy. In addition, the NO therapy was associated with an improvement in some neuropsychological parameters pertaining to verbal memory and nonverbal problem solving. Our data show that ASA, in addition to being a classical urea-cycle disorder, is also a model of congenital human NO deficiency and that ASA subjects could potentially benefit from NO supplementation. Hence, NO supplementation should be investigated for the long-term treatment of this condition. PMID:22541557

Nagamani, Sandesh C S; Campeau, Philippe M; Shchelochkov, Oleg A; Premkumar, Muralidhar H; Guse, Kilian; Brunetti-Pierri, Nicola; Chen, Yuqing; Sun, Qin; Tang, Yaoping; Palmer, Donna; Reddy, Anilkumar K; Li, Li; Slesnick, Timothy C; Feig, Daniel I; Caudle, Susan; Harrison, David; Salviati, Leonardo; Marini, Juan C; Bryan, Nathan S; Erez, Ayelet; Lee, Brendan



Nitric-Oxide Supplementation for Treatment of Long-Term Complications in Argininosuccinic Aciduria  

PubMed Central

Argininosuccinate lyase (ASL) is required for the synthesis and channeling of L-arginine to nitric oxide synthase (NOS) for nitric oxide (NO) production. Congenital ASL deficiency causes argininosuccinic aciduria (ASA), the second most common urea-cycle disorder, and leads to deficiency of both ureagenesis and NO production. Subjects with ASA have been reported to develop long-term complications such as hypertension and neurocognitive deficits despite early initiation of therapy and the absence of documented hyperammonemia. In order to distinguish the relative contributions of the hepatic urea-cycle defect from those of the NO deficiency to the phenotype, we performed liver-directed gene therapy in a mouse model of ASA. Whereas the gene therapy corrected the ureagenesis defect, the systemic hypertension in mice could be corrected by treatment with an exogenous NO source. In an ASA subject with severe hypertension refractory to antihypertensive medications, monotherapy with NO supplements resulted in the long-term control of hypertension and a decrease in cardiac hypertrophy. In addition, the NO therapy was associated with an improvement in some neuropsychological parameters pertaining to verbal memory and nonverbal problem solving. Our data show that ASA, in addition to being a classical urea-cycle disorder, is also a model of congenital human NO deficiency and that ASA subjects could potentially benefit from NO supplementation. Hence, NO supplementation should be investigated for the long-term treatment of this condition.

Nagamani, Sandesh C.S.; Campeau, Philippe M.; Shchelochkov, Oleg A.; Premkumar, Muralidhar H.; Guse, Kilian; Brunetti-Pierri, Nicola; Chen, Yuqing; Sun, Qin; Tang, Yaoping; Palmer, Donna; Reddy, Anilkumar K.; Li, Li; Slesnick, Timothy C.; Feig, Daniel I.; Caudle, Susan; Harrison, David; Salviati, Leonardo; Marini, Juan C.; Bryan, Nathan S.; Erez, Ayelet; Lee, Brendan



Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention - a retrospective nationwide cohort study  

Microsoft Academic Search

BACKGROUND: The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention. MATERIALS AND METHODS: All patients aged 30

Casper H Jørgensen; Gunnar H Gislason; Charlotte Andersson; Ole Ahlehoff; Mette Charlot; Tina K Schramm; Allan Vaag; Steen Z Abildstrøm; Christian Torp-Pedersen; Peter R Hansen



Role of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion.  


We studied the involvement of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. Feline middle cerebral arteries were prepared from control animals killed under anesthesia and from anesthetised animals subjected to hemorrhagic hypotension (stepwise bleeding to 90, 70, and 50 mmHg, maintained for 20 min at each level) followed by retransfusion (20 min). Two-mm-long vessel segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. Contractions to noradrenaline (norepinephrine), relaxations to acetylcholine, ATP, adenosine, and SIN-1, a nitric oxide donor compound, were compared in the vessels of the control and hemorrhage-subjected animals. Contractile responses to noradrenaline were significantly enhanced after hemorrhage, whereas relaxations to acetylcholine, ATP, and adenosine were significantly reduced. Relaxations to SIN-1, however, remained unchanged. L-Arginine did not cause relaxations in control vessels but relaxed the arteries after hemorrhage and retransfusion. To clarify the involvement of the L-arginine-nitric oxide pathway in these alterations, we studied the effect of exogenous application of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF) and NG-nitro-L-arginine (NOLA), a competitive antagonist of the EDRF-producing enzyme on the vascular responses in vitro. Similar to the effect of hypotension and retransfusion, NOLA enhanced the noradrenaline-induced contractions and inhibited the acetylcholine-induced and purinoceptor-mediated relaxations in the control arteries. In the control vessels in vitro, L-arginine treatment did not modify any contractile or relaxant response. At the same time, in vitro L-arginine treatment inhibited the hemorrhagic hypotension-induced enhancement of the contractions to noradrenaline and restored the diminished relaxations to acetylcholine (but not to ATP or adenosine). In the vessels after hemorrhage, NOLA neither further enhanced the already markedly enhanced noradrenaline-induced contractions nor further inhibited the relaxations caused by ATP and adenosine. In the case of acetylcholine, however, NOLA caused a further inhibition of the relaxations. The effect of in vivo L-Arg infusion (30 mg/kg initial bolus and 10 mg/kg/min infusion) during hemorrhagic hypotension and retransfusion on the in vitro vascular reactivity was similar to that of the in vitro L-arginine treatment. The present study demonstrates that even short-lasting hemorrhagic hypotension combined with retransfusion markedly inhibits nitric oxide-mediated, agonist-induced endothelium-dependent cerebrovascular responses. In vivo or in vitro L-arginine treatment is able to restore normal responses to some agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1446389

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



Foreign Currency for Long-Term Investors  

Microsoft Academic Search

Conventional wisdom holds that conservative investors should avoid exposure to foreign currency risk. Even if they hold foreign equities, they should hedge the currency exposure of these positions and hold only domestic Treasury bills. This paper argues that the conventional wisdom may be wrong for long-term investors. Domestic bills are risky for long-term investors, because real interest rates vary over

John Y. Campbell; Luis M. Viceira; Joshua S. White



Buying Long-Term Care Insurance  


... you can afford the long-term care insurance policy over time, as your monthly income may change Research and consider different options and talk with a professional before finalizing your decision Don’t feel pressured into making a decision LTC PathFinder Long-term care is ...


Long Term Preservation of Digital Information.  

ERIC Educational Resources Information Center

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…

Lorie, Raymond A.


Conditions for Gaussian long term manufacturing processes  

Microsoft Academic Search

The manufacturing community defines capability indices for manufacturing processes applicable time-wise for both long term and short term processes. The long term process distribution can be constructed from the consolidation of the data sets that was used to estimate the multiple short term distributions. There is a tendency for Gaussian distributed short-term processes to exhibit time sensitive random variation in

R. J. Pieper; Nikhil T. Satyala



Cardiac hypoxia and subsequent reoxygenation: sensitivity to L-arginine methylester.  

PubMed Central

The effect of L-arginine methylester (L-Arg-Me) was studied in the isolated heart of the guinea-pig perfused with hypoxic substrate-free medium for 30 min and subsequently reoxygenated with normal saline solution for 30 min. The administration of L-Arg-Me in basal conditions decreases dose-dependently heart rate without any changes in the myocardial structure. On the other hand, the administration of L-Arg-Me (5-10 mM) decreases ventricular arrhythmias, especially during reoxygenation; in fact ventricular fibrillation is abolished. L-Arg-Me treatment increases the recovery of normal electrical and mechanical activity at the end of reoxygenation and reduces the increase in basal tone. Treatment with 10 mM L-Arg-Me decreases lactate dehydrogenase (LDH) release in the effluent and lysosomal fragility in cardiac tissue, while it does not influence calcium gain. L-Arginine (L-Arg) does not mimic any of the effects of L-Arg-Me. Images Figure 2

Baccaro, C.; Bennardini, F.; Dini, G.; Franconi, F.; Giotti, A.; Matucci, R.; Minuti, P.



Cardiac hypoxia and subsequent reoxygenation: sensitivity to L-arginine methylester.  


The effect of L-arginine methylester (L-Arg-Me) was studied in the isolated heart of the guinea-pig perfused with hypoxic substrate-free medium for 30 min and subsequently reoxygenated with normal saline solution for 30 min. The administration of L-Arg-Me in basal conditions decreases dose-dependently heart rate without any changes in the myocardial structure. On the other hand, the administration of L-Arg-Me (5-10 mM) decreases ventricular arrhythmias, especially during reoxygenation; in fact ventricular fibrillation is abolished. L-Arg-Me treatment increases the recovery of normal electrical and mechanical activity at the end of reoxygenation and reduces the increase in basal tone. Treatment with 10 mM L-Arg-Me decreases lactate dehydrogenase (LDH) release in the effluent and lysosomal fragility in cardiac tissue, while it does not influence calcium gain. L-Arginine (L-Arg) does not mimic any of the effects of L-Arg-Me. PMID:3708203

Baccaro, C; Bennardini, F; Dini, G; Franconi, F; Giotti, A; Matucci, R; Minuti, P



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

NASA Astrophysics Data System (ADS)

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.

Makela, Anu M.



Cerebral Endothelial Function Determined by Cerebrovascular Reactivity to L-Arginine  

PubMed Central

Endothelium forms the inner cellular lining of blood vessels and plays an important role in many physiological functions including the control of vasomotor tone. Cerebral endothelium is probably one of the most specific types but until recently it was impossible to determine its function. In this review, the role of cerebrovascular reactivity to L-arginine (CVR-L-Arg) for assessment of cerebral endothelial function is discussed. L-Arginine induces vasodilatation through enhanced production of nitric oxide (NO) in the cerebral endothelium. Transcranial Doppler sonography is used for evaluation of cerebral blood flow changes. The method is noninvasive, inexpensive, and enables reproducible measurements. CVR-L-Arg has been compared to flow-mediated dilatation as a gold standard for systemic endothelial function and intima-media thickness as a marker for morphological changes. However, it seems to show specific cerebral endothelial function. So far CVR-L-Arg has been used to study cerebral endothelial function in many pathological conditions such as stroke, migraine, etc. In addition CVR-L-Arg has also proven its usefulness in order to show potential improvement after pharmacological interventions. In conclusion CVR-L-Arg is a promising noninvasive research method that could provide means for evaluation of cerebral endothelial function in physiological and pathological conditions.

Pretnar-Oblak, Janja



Spectroscopic and thermal studies of L-arginine doped Potassium Dihydrogen Phosphate crystals  

NASA Astrophysics Data System (ADS)

We have used IR transmission and Raman spectroscopy to study the active doping of potassium dihydrogen phosphate (KDP) crystals with L-arginine amino acid. In the present investigation, pure and doped KDP crystals were grown by slow evaporation solution method. Although the dominant bands observed in the infrared absorption spectra correspond to KDP crystals, the existence of vibrational lines at 1401 cm-1 (CH2), 1637 cm-1 (COO^-), 1716 cm-1 (NH3^+), and 3127 cm-1 (NH3^+) indicate that successful doping was achieved. This affirmation is further corroborated by the FT-Raman data, where strong lines are observed in the 2800 cm-1 -- 3100 cm-1 region, which is associated with C-H stretching modes of amino acids. The crystal structure and the thermal stability of the samples were also examined by powder X-ray diffraction and thermogravimetric techniques, respectively. Thermogravimetric analysis demonstrates a decrease of the thermal stability with increasing doping amount. An increase of second harmonic generation efficiency was found with more L-Arginine doping.

Govani, Jayesh; Manciu, Felicia; Joshi, Mihir; Parikh, Ketan; Dave, Dipak



NG-Monomethyl-l-arginine co-injection attenuates the thermogenic and hyperthermic effects of E2 prostaglandin microinjection into the anterior hypothalamic preoptic area in rats  

Microsoft Academic Search

Prostaglandin E 2 (PGE2) microinjection (25 ng, 250 hi) into the preoptic area of the anterior hypothalamus (POAH) stimulated heat production in brown adipose tissue (BAT) and increased core temperature in urethane-anesthetized rats. These thermogenic and hyperthermic effects were attenuated by co-injection of N°-monomethyl-L-arginine (NMMA, 25\\/~g), a competitive inhibitor of nitric oxide (NO) production from L-arginine. Inclusion of L-arginine (50\\/zg),

Shimon Amir; E DEBLASIO; Ann M. English



L-Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia\\/Reperfusion Injury in Skeletal Muscle  

Microsoft Academic Search

Background Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia\\/reperfusion (I\\/R) injury: NO in the presence of sufficient L-arginine and superoxide at the diminished local L-arginine concentration accompanying I\\/R. Methods and Results During hindlimb I\\/R (2.5 hours\\/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and L-arginine (chromatography), superoxide (chemiluminescence), and I\\/R injury were measured intermittently. Normal

Igor Huk; Joseph Nanobashvili; Christoph Neumayer; Andreas Punz; Markus Mueller; Kaweh Afkhampour; Martina Mittlboeck; Udo Losert; Peter Polterauer; Erich Roth; Stephen Patton; Tadeusz Malinski



Long-Term Intravesical Oxybutynin Chloride Therapy in Children with Myelodysplasia  

Microsoft Academic Search

PurposeWe evaluated the clinical use of long-term intravesical oxybutynin chloride in the treatment of neurogenic bladder dysfunction in children with myelodysplasia who could not tolerate oral anticholinergics.

Kelly A. Painter; Thomas S. Vates; Timothy P. Bukowski; Patricia Fleming; Andrew L. Freedman; Craig A. Smith; Ricardo Gonzalez; Alan D. Perlmutter



The first Robert Furchgott lecture: from endothelium-dependent relaxation to the L-arginine:NO pathway.  


Nitric oxide (NO) is released from vascular endothelial cells and fresh vascular tissue in amounts sufficient to account for the biological actions of endothelium-derived relaxing factor. It is synthesized from the terminal guanidino nitrogen atom(s) of L-arginine, a process that is inhibited by NG-monomethyl-L-arginine (L-NMMA). Studies using L-NMMA have shown that NO is constantly generated by the vessel wall to maintain vasodilator tone. The L-arginine:NO pathway has now been identified in a number of other cells and tissues, in many of which it acts as the transduction mechanism for stimulation of the soluble guanylate cyclase. PMID:1978693

Moncada, S



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


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. PMID:20682460

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



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

PubMed Central

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 ?mol/L/24 h (95% confidence interval [CI], 9–13 ?mol/L/24 h), from a baseline of 49 ?mol/L (95% CI, 37–45 ?mol/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.

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.



Dual effect of nickel on L-arginine/nitric oxide system in RAW 264.7 macrophages.  


The immunogenic mechanisms of the potent contact allergen nickel are not completely clear. Nitric oxide (NO) serves as a fundamental signalling and effector molecule in the immune system, but little is known about its possible role in immune reactions elicited by nickel. We investigated the effects of nickel on the L-arginine/inducible NO synthase (iNOS) system in a murine macrophage cell line, RAW 264.7. Both LPS-stimulated and non-stimulated RAW 264.7 cells were incubated in the presence of 0-100 ?M nickel sulphate for 24 h. Subsequently, NO production, iNOS protein expression, L-arginine uptake and gene expression of iNOS and cationic amino acid transporter systems (CAT) were measured. We found that 100 ?M NiSO4 increased LPS-induced nitrite production as well as the formation of [(3)H]-L-citrulline from [(3)H]-L-arginine in the RAW 264.7 cells. Correspondingly, the expression of iNOS gene and protein was also remarkably enhanced. Nevertheless, nickel had an inhibitory effect on L-arginine transport which disappeared gradually upon LPS-stimulation in parallel with an increase in NO output. LPS was found to significantly amplify CAT-3 as well as CAT-2 mRNA expression, mirroring the increase in L-arginine transport. In the range of 1-10 ?M, NiSO4 did not have any additional effect on CAT mRNA expression, but at 100 ?M it was able to enhance CAT-1 and CAT-3 mRNA expression upon LPS stimulation. Our data indicate that nickel interferes with macrophages' L-arginine/NOS system on multiple levels. Considering the potent biological effects of NO, these influences may contribute to nickel toxicity. PMID:23415871

Volke, Annika; Rünkorg, Kertu; Wegener, Gregers; Vasar, Eero; Volke, Vallo



Isotopic study of L-Arginine kinetics in the lung during pseudomonas sepsis in an ovine model  

PubMed Central

The objective of the study is to investigate how L-Arginine pulmonary metabolism is altered in response Pseudomonas aeruginosa (P. aeruginosa) induced septic conditions using an ovine model. Methods: Seven female sheep were infused with a primed-constant infusion of L-[15N2-guanidino, 5, 5, 2H2] L-Arginine for 28 hs. After the initial 4 hs of the L-Arginine infusion, a continuous infusion of live Pseudomonas aeruginosa bacteria started for 24 hs. A NO synthase (NOS) inhibitor, NG-Methyl-L-arginine (L-NMA), infusion was added during the last 4 hs of the bacterial infusion. Blood samples were taken at specific time points for isotopic enrichment during control, septic and NOS blocking phases of the study. Results: We observed that the level of total delivery of L-Arginine to the lungs was significantly decreased in septic phase after 24 hours of pseudomonas infusion. In contrast, the fractional uptake and metabolism of L-Arginine by the lungs was doubled during septic phase relative to the control phase (MARG-basal = 100% vs. MARG-septic = 220 ± 56%, P < 0.05). NO production in the lungs was also significantly increased. Infusion of L-NMA markedly blunted this elevated NO production and attenuated the total arginine metabolized in the septic lungs (Mnitrate-septic = 43.6 ± 5.7 vs. Mnitrate-septic + L-NMA = 13.4 ± 5.1 umol/kg/min; p < 0.05). We demonstrated sepsis induced by P. aeruginosa infusion caused an increase in the fractional uptake and metabolic rate of arginine in the lungs. Furthermore, our data suggests that arginine was mainly consumed via arginine – NO pathway, which might be responsible for this enhanced arginine metabolic activity in the septic lungs.

Xu, Hongzhi; Watson, Davin; Yu, Yong-Ming; Traber, Daniel L; Fischer, Stefani; Nichols, Joan; Deyo, Donald; Traber, Lillian L; Cortiella, Joaquin



The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists.  


L-arginine may enhance endurance performance mediated by two primary mechanisms including enhanced secretion of endogenous growth hormone (GH) and as a precursor of nitric oxide (NO); however, research in trained participants has been equivocal. The purpose was to investigate the effect of acute L-arginine ingestion on the hormonal and metabolic response during submaximal exercise in trained cyclists. Fifteen aerobically trained men (age: 28 ± 5 y; body mass: 77.4 ± 9.5 kg; height: 180.9 ± 7.9 cm; VO2max: 59.6 ± 5.9 ml·kg- 1·min-1) participated in a randomized, double-blind, crossover study. Subjects consumed L-arginine (ARG; 0. 075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of submaximal exercise (60 min at 80% of power output achieved at ventilatory threshold). The ARG condition significantly increased plasma L-arginine concentrations (~146%), while no change was detected in the PLA condition. There were no differences between conditions for GH, nonesterified fatty acids (NEFA), lactate, glucose, VO2, VCO2, RER, CHO oxidation, and NOx. There was reduced fat oxidation at the start of exercise (ARG: 0.36 ± 0.25 vs. PLA: 0.42 ± 0.23 g·min-1, p < .05) and an elevated plasma glycerol concentrations at the 45-min time point (ARG: 340.3 vs. PLA: 288.5 ?mol·L-1, p < .05) after L-arginine consumption. In conclusion, the acute ingestion of L-arginine did not alter any hormonal, metabolic, or cardio-respiratory responses during submaximal exercise except for a small but significant increase in glycerol at the 45-min time point and a reduction in fat oxidation at the start of exercise. PMID:23319437

Forbes, Scott C; Harber, Vicki; Bell, Gordon J



Synthesis of nitric oxide from the two equivalent guanidino nitrogens of L-arginine by Lactobacillus fermentum.  

PubMed Central

Ten strains of Lactobacillus fermentum that differed in origin converted metmyoglobin to nitrosylmyoglobin [a pentacoordinate nitric oxide (NO) complex of Fe(II) myoglobin] in MRS broth at pH 4.3. Of the 10 strains, L. fermentum IFO 3956 possessed the strongest capacity to convert metmyoglobin to nitrosylmyoglobin. This strain synthesizes NO enzymatically from the two equivalent guanidino nitrogens of L-arginine. To our knowledge, this demonstrates for the first time the production of NO synthesized from the guanidino nitrogens of L-arginine by lactic acid bacteria. IFO 3956 may possess a bacterial NO synthase.

Morita, H; Yoshikawa, H; Sakata, R; Nagata, Y; Tanaka, H



Solubility and dissolution kinetics of calcium oxalate renal calculi in solutions containing L-arginine: In-vitro experiments  

NASA Astrophysics Data System (ADS)

The kinetics of dissolution of calcium oxalate (CaOX) calculi in physiological solutions containing L-arginine at different concentrations were studied using the change in the Archimedean weight of samples immersed in the solution. It was faound that arginine, which is a normal constituent of human urine, acts at increased concentrations as a dissolving agent with respect to CaOX calculi. The possible effect of L-arginine as a natural regulator of CaOX supersaturation and crystalization in human urine is also disscused.

Atanassova, S.



Growth and characterization of nonlinear optical crystal zinc tris (thiourea) sulphate in presence of L-arginine  

NASA Astrophysics Data System (ADS)

The present communication deals with the single crystal growth and characterization of zinc tris (thiourea) sulphate (ZTS) doped with different molar concentrations of basic amino acid L-arginine. Doped single crystals of ZTS were grown by solvent evaporation method at constant temperature (35 °C). Doped crystals exhibit prominent morphological changes in different crystallographic planes. Incorporation of L-arginine in ZTS crystals has been estimated qualitatively by Fourier transformed infrared spectra. Lattice parameters were determined by powder X-ray diffraction analysis. The influence of the organic impurity on optical and mechanical properties has also been studied.

Moitra, Sweta; Kar, Tanusree



What Is Long-Term Care?  


... Term Care? Expand Long-term Care Considerations for LGBT Adults Expand Health Disparities Impacting LTC Expand Caregivers ... on Alzheimer's Disease Lesbian, Gay, Bisexual and Transgender (LGBT) community Home About Us Accessibility Disclaimer Privacy Contact ...


Who Needs Care? (Long-Term Care)  


... Term Care? Expand Long-term Care Considerations for LGBT Adults Expand Health Disparities Impacting LTC Expand Caregivers ... on Alzheimer's Disease Lesbian, Gay, Bisexual and Transgender (LGBT) community Home About Us Accessibility Disclaimer Privacy Contact ...


Administration in Long Term Care Facilities.  

National Technical Information Service (NTIS)

The proceedings of a seminar on strategies for improving long-term care facilities through better management are reported. Forms for use in the identification of goals, problem areas, and management practices are included. An intersystem approach to long-...



Long Term Cryopreservation of Dog Granulocytes.  

National Technical Information Service (NTIS)

Granulocytes isolated by counterflow centrifugation eluriation (CCE) from leukapheresed dog blood, frozen in liquid nitrogen at -196 C, were studied. The effects of long term cryopreservation on cell recovery and in vitro function were determined. In eigh...

F. J. Lionetti F. W. Luscinskas C. R. Valeri A. J. Melaragno



Long-Term Use of Benzodiazepines  

PubMed Central

Problems associated with physical dependence and abuse of benzodiazepines by a small percentage of patients have reduced their popularity from the most commonly prescribed psychoactive drug in the 1970s to being prescribed for mainly short periods. Patients who benefit from long-term benzodiazepine use are nearly ignored by the medical community as a whole. This article details what patient population can improve from long-term benzodiazepine therapy, the risks and benefits of treatment, and how to select appropriate candidates.

Potts, Nicholas L.S.; Krishnan, K. Ranga R.



Evidence-based long term care design.  


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. PMID:19893184

Calkins, Margaret P



Who Should Buy Long-Term Bonds?  

Microsoft Academic Search

According to conventional wisdom, long-term bonds are appropriate for conservative long-term investors. This paper develops a model of optimal consumption and portfolio choice for infinite-lived investors with recursive utility who face stochastic interest rates, solves the model using an approximate analytical method, and evaluates conventional wisdom. As risk aversion increases, the myopic component of risky asset demand disappears but the

John Y. Campbell; Luis M. Viceira



Preceptors in long-term care  

Microsoft Academic Search

A preceptor is an experienced and competent staff member who serves as a clinical role model and resource person to newly employed nursing personnel. Although this concept has been prominent since the late 1970s in acute health care settings, preceptors rarely are used in long-term care facilities. This article describes the overall effectiveness of the first long-term care preceptor program

Cindy A Shemansky



Classification of Long-Term EEG Recordings  

Microsoft Academic Search

\\u000a Computer assisted processing of long-term EEG recordings is gaining a growing importance. To simplify the work of a physician,\\u000a that must visually evaluate long recordings, we present a method for automatic processing of EEG based on learning classifier.\\u000a This method supports the automatic search of long-term EEG recording and detection of graphoelements – signal parts with characteristic\\u000a shape and defined

Karel Kosar; Lenka Lhotská; Vladimir Krajca



Long-Term Property Insurance 1  

Microsoft Academic Search

This paper proposes long-term insurance (LTI) as an alternative to the standard annual property insurance policy. LTI offers significant benefits to many stakeholders by reducing insurers' administrative costs, lowering search costs, providing stability to consumers and incentivizing property owners to invest in risk-reducing measures. A simple two-period model illustrates situations that would make a long-term contract attractive to both insurers

Dwight Jaffee; Howard Kunreuther; Erwann Michel-Kerjan


Physicochemical and molecular modeling studies of cefixime-L-arginine-cyclodextrin ternary inclusion compounds.  


In an attempt to improve the physicochemical properties of cefixime (CEF), its supramolecular inclusion compounds were prepared with ?-cyclodextrin (?CD) and hydroxypropyl-?-cyclodextrin (HP?CD) in presence and/or absence of ternary component L-arginine (ARG) using spray drying technique. Initially, the phase solubility studies revealed a stoichiometry of 1:1 molar ratio with an AL-type of phase solubility curve. The stability constants of binary systems were remarkably improved in presence of ARG, indicating positive effect of its addition. The inclusion complexes were characterized by FTIR, XRPD, DSC, SEM, particle size analysis, and dissolution studies. Further, molecular mechanic (MM) calculations were performed to investigate the possible orientations of CEF inside ?CD cavity in presence and/or absence of ternary component. In case of physicochemical studies, the ternary systems performed well as a result of comprehensive effect of ternary complexation and particle size reduction achieved by a spray drying technology. PMID:24053809

Jadhav, Priyanka; Petkar, Bhushan; Pore, Yogesh; Kulkarni, Anita; Burade, Kishorkumar



Characterization studies on the additives mixed L-arginine phosphate monohydrate (LAP) crystals  

NASA Astrophysics Data System (ADS)

L-arginine phosphate monohydrate (LAP), potassium thiocyanate (KSCN) mixed LAP (LAP:KSCN) and sodium sulfite (Na 2SO 3) mixed LAP (LAP:Na 2SO 3) single crystals were grown by slow cooling technique. The effect of microbial contamination and coloration on the growth solutions was studied. The crystalline powders of the grown crystals were examined by X-ray diffraction and the lattice parameters of the crystals were estimated. From the FTIR spectroscopic analysis, various functional group frequencies associated with the crystals were assigned. Vickers microhardness studies were done on {1 0 0} faces for pure and additives mixed LAP crystals. From the preliminary surface second harmonic generation (SHG) results, it was found that the SHG intensity at (1 0 0) face of LAP:KSCN crystal was much stronger than that of pure LAP.

Haja Hameed, A. S.; Karthikeyan, C.; Ravi, G.; Rohani, S.



Diamond turning of L-arginine phosphate, a new organic crystal  

SciTech Connect

We have demonstrated that single point diamond turning can be used to generate high optical quality finished surfaces on a new organic nonlinear crystal, L-arginine phosphate (LAP). The proper choice of cutting conditions can produce surfaces with {lt}5-A rms local roughness. Local softening or melting near the cutting tool tip may play a key role in the machining process by ensuring that material is removed by ductile cutting rather than brittle fracture. At the same time, the low melting temperature of LAP makes lubrication and cooling especially important to prevent extensive melting and tool fouling. In spite of the presence of a weak cleavage plane in LAP, the surface quality is relatively insensitive to crystallographic orientation. Tool wear is apparently negligible, so that surface flatness is governed by the stability of the diamond turning machine. These results suggest that it may be possible to fabricate large aperture LAP harmonic converters for use in inertial confinement fusion lasers.

Fuchs, B.A.; Syn, K.; Velsko, S.P. (Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94550 (US))



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

NASA Technical Reports Server (NTRS)

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.

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



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

PubMed Central

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.

Boudko, Dmitri Y.



Asymmetric dimethylarginine (ADMA) and L-arginine levels in children with glycogen storage disease type I.  


Patients with glycogen storage disease type I (GSD-I) often have marked hyperlipidemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy; therefore, these patients may be at high risk for the development of atherosclerosis. A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), a naturally occuring product of asymmetric methylation of proteins, is an endogenous inhibitor of endothelial nitric oxide synthase. ADMA causes endothelial dysfunction, vasoconstriction, blood pressure elevation, atherosclerosis, and kidney disease progression. A high prevalence of elevated plasma ADMA levels is observed in adults with hypercholesterolemia, hypertension, chronic kidney disease, diabetes mellitus, peripheral arterial disease, coronary artery disease, preeclampsia, heart failure, liver disease, stroke, and many other clinical disorders. Therefore, we aimed to evaluate the endothelial function in patients with GSD-I by using ADMA levels. High-performance liquid chromatography - based method was used for measuring ADMA and L-arginine levels in plasma. The ADMA level was similar between children with GSD-I and the age-matched healthy control group (0.9±0.28 vs. 1.1±0.45 ?mol/L; p=0.18). The L-arginine plasma levels in patients with GSD-I were found to be 55.7±41.3 and 91.6±50.2 ?mol/L in healthy controls. The preservation of normal endothelial function may result from diminished platelet aggregation, increased levels of apolipoprotein E, decreased susceptibility of low-density lipoprotein to oxidation (possibly related to the altered lipoprotein fatty acid profile in GSD-I), and increased antioxidative defenses in plasma protecting against lipid peroxidation. PMID:23412857

Kasapkara, Çi?dem Seher; Tümer, Leyla; Biberoglu, Gursel; Kasapkara, Ahmet; Hasano?lu, Alev



Does l-arginine availability during the early pregnancy alters the immune response of Trypanosoma cruzi infected and pregnant Wistar rats?  


Chagas disease induces a strong immune response and l-arginine is an essential amino acid which plays an important role in homeostasis of the immune system. The aims of this study were to evaluate parasitemia, corticosterone levels, production of nitric oxide (NO), fetal morphological measurements, and histology of heart and placenta. Twenty pregnant Wistar rats (180-220g) were grouped in: pregnant control (PC), pregnant control and l-arginine supplied (PCA), pregnant infected (PI), pregnant infected and l-arginine supplied (PIA). Females were infected with 1×10(5) trypomastigotes of the Y strain (3rd day of pregnancy). Animals were supplied with 21mg of l-arginine/kg/day during 14days. PIA showed significant decreased levels of corticosterone and parasitemia. For control groups, any alteration in NO production was found with l-arginine supplementation; for PIA, enhanced nitrite concentrations were observed as compared to PI. Weights and lengths of fetuses were higher in l-arginine treated and infected pregnant rats as compared to untreated ones. Placental weight from the PIA group was significantly increased when compared to PI. In l-arginine treated animals, cardiac tissue showed reduced amastigote burdens. PIA and PI displayed similar placental parasitism. Based on these results, l-arginine supplementation may be potentially useful for the protection against Trypanosoma cruzi during pregnancy. PMID:24786713

da Costa, Cássia Mariana Bronzon; de Freitas, Murilo Rodrigues Barbosa; Brazão, Vânia; Dos Santos, Carla Domingues; Sala, Miguel Angel; do Prado Júnior, José Clovis; Abrahão, Ana Amélia Carraro



Reduction of platelet thrombi and emboli by L-arginine during cardiopulmonary bypass in a pig model  

Microsoft Academic Search

We wanted to test the hypothesis that NO generation by L-arginine (LA) infusion will be beneficial in increasing blood flow to all organs to counteract the process of global ischemia during cardiopulmonary bypass (CPB) and to reduce platelet emboli by platelet inhibition. The effect of LA infusion on NO formation, vasodilation, and reduction of thromboembolic burden in organs and tissues

Mrinal K. Dewanjee; Shu Ming Wu; Mansoor Kapadvanjwala; Dibyendu De; Sumit Dewanjee; Stana Novak; Li-Chien Hsu; Richard A. Perryman; Aldo N. Serafini; George N. Sfakianakis; Robert C. Duncan; W. Dalton Dietrich; Allan F. Horton



Molecular Plasticity of Vascular Wall During NG-Nitro-L-Arginine Methyl Ester-Induced Hypertension Modulation of Proinflammatory Signals  

Microsoft Academic Search

It has previously been reported that hypertension induced by the chronic blockade of NO production is characterized by a proinflammatory phenotype of the arterial wall associated with a periarterial accumulation of inflammatory cells. In the present study, the cellular and molecular mechanisms involved in the luminal and perivascular accumulation of inflammatory cells were evaluated in the aortas of NG-nitro-L-arginine methyl

Walter Gonzalez; Vincent Fontaine; Maria E. Pueyo; Nathalie Laquay; David Messika-Zeitoun; Monique Philippe; Jean-Francois Arnal; Marie-Paule Jacob; Jean-Baptiste Michel


Effects of l-arginine and creatine administration on spatial memory in rats subjected to a chronic variable stress model.  


Abstract Context: Chronic stress results from repeated exposure to one or more types of stressors over a period, ranging from days to months, and can be associated with physical, behavioral, and neuropsychiatric manifestations. Some physiological alterations resulting from chronic stress can potentially cause deficits on spatial learning and memory. Objective: This study investigated the effects of chronic variable stress (CVS) and administration of l-arginine and creatine on spatial memory in rats. Furthermore, body, heart, adrenal weight, and plasma glucose and corticosterone levels were analyzed. Material and methods: Male Wistar rats were subjected to a CVS model for 40 days and evaluated for spatial memory after the stress period. Chronically stressed animals were treated daily by gavage with: 0.5% carboxymethylcellulose (Group Cs), 500?mg/kg l-arginine (Group Cs/La), 300?mg/kg creatine (Group Cs/Cr); and 500?mg/kg l-arginine and 300?mg/kg creatine (Group Cs/La + Cr) during the entire experimental period. Results: Our results showed that animals in the Cs/Cr and Cs/La + Cr groups presented significantly decreased corticosterone levels compared to group Cs (p?l-arginine, improves reference memory retention, a phenomenon that is possibly associated with increased creatine/phosphocreatine levels and l-arginine-derived NO synthesis. PMID:24617967

Dos Santos, Fabio Seidel; da Silva, Luiz Augusto; Pochapski, José Augusto; Raczenski, Alan; da Silva, Weber Claudio; Grassiolli, Sabrina; Malfatti, Carlos Ricardo Maneck



The long-term ecological research program  

NASA Astrophysics Data System (ADS)

Major developments have emerged in the field of ecology as a result of taking a long-term approach to both basic and applied research [Strayer, 1986]. In recognition of both the advantages of long-term research programs and the historical difficulty of sustaining such research efforts, the National Science Foundation (NSF) instituted its Long-Term Ecological Research (LTER) Program in 1980 [Callahan, 1984]. The LTER Program has a number of important links with the geosciences and is likely to play a significant role in work on terrestrial, freshwater, and estuarine ecosystems within the International Geosphere-Biosphere Program (IBGP); it is thus a good time for us to begin communicating with geoscientists who are helping to shape IGBP.

Swanson, Frederick J.; Franklin, J. F.


The US Long Term Ecological Research Program  

NSDL National Science Digital Library

This peer-reviewed article from BioScience describes Long Term Ecological Research program in the US. The 24 projects of the National Science Foundation's Long Term Ecological Research Network, whose sites range from the poles to the Tropics, from rain forests to tundras and deserts, and from offshore marine to estuarine and freshwater habitats, address fundamental and applied ecological issues that can be understood only through a long-term approach. Each project addresses different ecological questions; even the scale of research differs across sites. Projects in the network are linked by the requirement for some research at each site on five core areas, including primary production, decomposition, and trophic dynamics, and by cross-site comparisons, which are aided by the universally available databases. Many species and environmental variables are studied, and a wide range of synthetic results have been generated.




Evaluation of the Prevalence of Chronic Kidney Disease and Rates of Oral Antidiabetic Prescribing in Accordance with Guidelines and Manufacturer Recommendations in Type 2 Diabetic Patients within a Long-Term Care Setting.  


This retrospective study assessed the prevalence of moderate to severe chronic kidney disease (CKD) among nursing home (NH) residents with type 2 diabetes. The pattern of oral antidiabetic drug (OAD) use and their concordance with the National Kidney Foundation (NKF) guideline and prescribing information (PI) was also assessed. About half (47%) of diabetic residents had moderate to severe CKD. A little over a quarter of the 186 residents using OADs received at least one NKF-discordant OAD prescription. Metformin was the most commonly misused OAD. PI nonconcordance was observed in 58.6% of residents and was highest in glipizide and metformin users. With the high prevalence of moderate to severe CKD in NH residents with diabetes, physicians should consider residents' renal function when choosing treatment plans and review treatments regularly to check compliance with the NKF guidelines or PIs. PMID:24719761

Wu, Ning; Yu, Xia; Greene, Mallik; Oderda, Gary



Evaluation of the Prevalence of Chronic Kidney Disease and Rates of Oral Antidiabetic Prescribing in Accordance with Guidelines and Manufacturer Recommendations in Type 2 Diabetic Patients within a Long-Term Care Setting  

PubMed Central

This retrospective study assessed the prevalence of moderate to severe chronic kidney disease (CKD) among nursing home (NH) residents with type 2 diabetes. The pattern of oral antidiabetic drug (OAD) use and their concordance with the National Kidney Foundation (NKF) guideline and prescribing information (PI) was also assessed. About half (47%) of diabetic residents had moderate to severe CKD. A little over a quarter of the 186 residents using OADs received at least one NKF-discordant OAD prescription. Metformin was the most commonly misused OAD. PI nonconcordance was observed in 58.6% of residents and was highest in glipizide and metformin users. With the high prevalence of moderate to severe CKD in NH residents with diabetes, physicians should consider residents' renal function when choosing treatment plans and review treatments regularly to check compliance with the NKF guidelines or PIs.

Wu, Ning; Greene, Mallik; Oderda, Gary



Bidding for Long-Term Care Patients.  

National Technical Information Service (NTIS)

This document outlines options for a long-term care system in which competitive bidding is used to establish the price of care. The design of the competitive bidding mechanism is examined along with the interaction and cross-impact of competitive bidding ...

A. J. Hogan C. V. Getts



Long-Term Recidivism of Child Molesters  

Microsoft Academic Search

We examined the long-term recidivism rates of 197 child molesters released from prison between 1958 and 1974. Overall, 42% of the total sample were reconvicted for sexual crimes, violent crimes, or both, with 10% of the total sample reconvicted 10–31 years after being released. Incest offenders were reconvicted at a slower rate than were offenders who selected only boys, with

R. Karl Hanson; Richard A. Steffy; Rene Gauthier




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...


Long-Term Monitoring of Polars  

NASA Astrophysics Data System (ADS)

We present long-term observations of magnetic cataclysmic variables AM Her, AN UMa, AR UMa, DP Leo, and V1309 Ori obtained with the ROTSEIIId telescope. All data have been analysed and preliminary results indicate periods of 170 days, 217 days, and 180 days for AM Her, AN UMa, and AR UMa, respectively.

Kalomeni, B.



Long-Term Stability of Social Participation  

ERIC Educational Resources Information Center

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…

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



Professionalism in Long-Term Care Settings  

ERIC Educational Resources Information Center

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…

Lubinski, Rosemary



Long-Term Care Research and Policy  

ERIC Educational Resources Information Center

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…

Kemper, Peter



Long-Term Impacts of Educational Interventions  

ERIC Educational Resources Information Center

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…

Deming, David James



Long-term opioid therapy reconsidered.  


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. PMID:21893626

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



Long-term studies of dopamine agonists.  


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. PMID:11909984

Hubble, Jean P




EPA Science Inventory

The Toxic Modeling System Long-Term (TOXLT) is a personal-computer- based model that has been developed in conjunction with the release of the new version of the EPAs Industrial Source Complex (ISC2) Dispersion Models (EPA, 1992) and the promulgation of the EPAs A Tiered Modeling...


Long-Term Sequelae of Stroke  

PubMed Central

Scant attention has been paid to the long-term consequences and complications resulting from a stroke. Many stroke survivors go on to develop a variety of medical, musculoskeletal, and psychosocial complications, years after the acute stroke. The family physician is regularly called upon to deal with these problems, but is often hampered by a lack of resources.

Teasell, Robert W.



Foundation work in long-term care.  


Health foundations have invested in services, research, and advocacy to improve the financing and delivery of long-term services and supports. This article describes some of the broad array of approaches they have taken--in such areas as aging in place, assisted living, "culture change" in nursing homes, quality improvement, augmenting the workforce, and paying for care. PMID:20048379

LeRoy, Lauren; Treanor, Katherine; Art, Emily




Microsoft Academic Search

Although the numbers of infants requiring dialysis are small, management of these patients presents many chal- lenges. Mortality is high in infants with comorbidities, com- plications of dialysis are common, and most of these infants need enteral feeding. However, the long-term outcome for otherwise healthy infants is comparable to that for older children.

Lesley Rees


Long Term Capability Requirements as derived from the Long Term Requirements Study  

Microsoft Academic Search

Of the 38 Long Term Capability Requirements indentified by NATO in the 2009 Long Term Requirements Study, at least four can be directly applied to waterside security research and technology. First, Area Access Control, the capability of controlling access to designated unattended areas and borders, denying or allowing access to appropriate personnel and equipment. It must be capable of monitoring

J. Brownlee



Long Term Care. Survey and Plan for Long Term Care in East Central Michigan.  

National Technical Information Service (NTIS)

A plan for development of facilities for long-term care in East Central Michigan is presented by East Central Michigan Comprehensive Health Planning Council (ECMCHPC) which is based on the findings of a survey of long-term care facilities. General plannin...



Long-term results after pancreas transplantation.  


With the advances in technique and immunosupression, not only the short- but the long-term outcomes of pancreas transplantation have improved significantly. This retrospective study describes the long-term outcomes of simultaneous pancreas and kidney (SPK) transplants, pancreas after kidney (PAK), and pancreas transplants alone (PTA). An overall analysis was performed for all deceased donor (DD) primary pancreas transplants performed in the United States between 1988 and 1999. In addition, the long-term outcome for pancreas transplants performed at the University of Minnesota (UM) was analyzed. For SPK transplants performed in the United States between 1998 and 1999, the half-life of the pancreas was almost 12 years, and was 12.5 years for kidneys. For SPK cases where the pancreas was functioning at 1 year, the half-lives of both the pancreas and the kidney grafts extended more than 14 years. The half-lives of solitary pancreas transplants were between 7 years for PAK and 9 years for PTA cases. For US solitary transplants with at least 1 year of graft function, the half-lives extended to almost 9 years. Pancreas transplants performed at the UM showed the same significant improvements over time. Of special interest is the excellent long-term graft function of pancreas transplants from a living donor, which in the early years clearly surpassed that of solitary DD pancreas transplants. A multivariate analysis showed that the factor with the highest impact on long-term graft function in all three transplant categories was the use of a young donor. In SPK cases, the most frequent reason for late graft loss was death with a functioning graft. In solitary pancreas transplants, most late graft losses were still due to immunological reasons. PMID:17889177

Sutherland, D E R; Gruessner, A C



Long-term consequences of severe infections.  


There are convincing data to show that the consequences of a severe infection extend well beyond the first month following it. During the first year after severe sepsis or infection, the survival of sepsis patients is guarded compared with matched control groups. Their quality of life is impaired, and they suffer from rapid degradation in cognition and functional capacity. We could postulate three explanations for the long-term bad outcomes of severe infections and sepsis (or a combination of the three): (i) sepsis usually happens in the elderly and sick, and it causes deterioration in life expectancy and functional status as an acute, non-specific event; (ii) an interaction between specific mechanisms of sepsis and underlying disorders; or (iii) long-term complications directly related to infection. If the second or third explanations are true, then management of the original infection/sepsis might have an influence on long-term outcomes. Elderly survivors of severe infections should be carefully assessed for whether they need intermediate care for recuperation and re-conditioning when leaving hospital. We need prospective, observational studies to define which are the factors that most influence long-term outcomes, and especially management of the acute infection. The investigation of long-term outcomes in trials of treatment modalities for sepsis or severe infections should be encouraged. The true answer for whether one treatment is better than another in severe infections or sepsis lies in the people trajectory in the year following the infection, and not only on 4-6 weeks outcome. PMID:23397980

Leibovici, L



Long-term survival of patients with pulmonary arterial hypertension recovering to World Health Organization functional class I or II: a historical comparison between intravenous epoprostenol and oral agents  

PubMed Central

Background Intravenous epoprostenol is the only drug proved in a randomized study to reduce mortality in patients with idiopathic pulmonary arterial hypertension (PAH). However, administration of this drug has procedural difficulties and a risk of sepsis. Oral drugs provide simple treatment, but their benefit for survival has not been proven. A recovery of patients with PAH to World Health Organization functional class (WHO-FC) I or II may predict favorable survival. Methods Survival analyses were performed on a historical cohort of 41 patients with PAH. The patients were 43?±?22 years old, 23 had idiopathic or heritable PAH, and 18 had connective tissue disease-associated PAH. The baseline was defined as the initial visit to a medical facility. Results The median duration of follow-up was 1276 days (108 to 5389 days) and 21 patients died during this period. The estimated survival times for patients who received intravenous epoprostenol and did and did not recover to WHO-FC I or II were 4371?±?577 days and 1172?±?404 days, respectively. These times for patients who were not treated with intravenous epoprostenol and did and did not recover to WHO-FC I or II were 4717?±?554 days and 925?±?230 days, respectively. A Cox proportional hazard analysis gave a hazard ratio for death after recovery to WHO-FC I or II of 0.07 (P?



Effect of L-arginine on HSP70 expression in liver in weanling piglets  

PubMed Central

Background This study was conducted to evaluate the effects of L-arginine (Arg) on photomicrographs and HSP70 expression in the liver of weanling piglets. Twelve healthy Landrace?×?Yorkshire piglets that had been weaned at 21 d (average body weight 5.56?±?0.51 kg) were randomly divided into a control group and an Arg group (6 g/kg feed). At age 28 d, all of the piglets were slaughtered to obtain liver samples to determine HSP70 expression by real-time PCR, western blot and immunohistochemistry. Results The results showed that, compared to control piglets, treatment with Arg decreased inflammatory reactions caused by weaning. The immunohistochemical localization of HSP70 in liver revealed strong expression in the Arg group. Arg increased HSP70 mRNA and HSP70 expression in the liver (P?



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

SciTech Connect

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

Servetnick, D.A.; Wiesenfeld, P.L.; Szepesi, B. (Univ. of Maryland, College Park (United States))



Binding-competent states for L-arginine in E. coli arginine repressor apoprotein.  


Arginine repressor of E. coli is a multifunctional hexameric protein that provides feedback regulation of arginine metabolism upon activation by the negatively cooperative binding of L-arginine. Interpretation of this complex system requires an understanding of the protein's conformational landscape. The ~50 kDa hexameric C-terminal domain was studied by 100 ns molecular dynamics simulations in the presence and absence of the six L-arg ligands that bind at the trimer-trimer interface. A rotational shift between trimers followed by rotational oscillation occurs in the production phase of the simulations only when L-arg is absent. Analysis of the system reveals that the degree of rotation is correlated with the number of hydrogen bonds across the trimer interface. The trajectory presents frames with one or more apparently open binding sites into which one L-arg could be docked successfully in three different instances, indicating that a binding-competent state of the system is occasionally sampled. Simulations of the resulting singly-liganded systems reveal for the first time that the binding of one L-arg results in a holoprotein-like conformational distribution. PMID:24952066

Pandey, Saurabh Kumar; Reha, David; Zayats, Vasilina; Melichercik, Milan; Carey, Jannette; Ettrich, Rüdiger



Effects of trimetazidine in acute pancreatitis induced by L-arginine  

PubMed Central

Background In acute pancreatitis, oxygen free radicals (OFRs) and cytokines have been shown to play a role in the failure of pancreatic microcirculation and the development of local tissue damage. We studied the effects of trimetazidine (TMZ), a potent antioxidant and anti-ischemic agent, on acute pancreatitis. Methods Rats were randomized into 3 groups: a control group (n = 15), a study group (n = 15) in which acute pancreatitis was induced with with L-arginine, and a treatment group (n = 15) in which pancreatitis was induced and treated with TMZ intraperitoneally. The rats were followed for 24 hours. At the 24th hour we determined serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, lactate dehydrogenase (LDH), interleukin 1-? (IL-1?), interleukin 6 (IL-6) and tumour necrosis factor-? (TNF-?), and the pancreatic tissues were analyzed histopathologically. Results The AST (p < 0.001), ALT (p < 0.01), amylase (p < 0.001), LDH (p < 0.01), TNF-? (p < 0.01), IL-1? (p < 0.001) and IL-6 (p < 0.001) levels, and pancreatic tissue edema (p < 0.01), hemorrhage (p < 0.05), acinar cell necrosis (p < 0.001) and level of perivascular inflammation (p < 0.01), were significantly lower in the treatment group than the study group. Conclusion Trimetazidine markedly decreases biochemical and histopathologic changes during the early stages of acute pancreatitis, thus preserving the pancreas histologically.

Yenicerioglu, Akan; Cetinkaya, Ziya; Girgin, Mustafa; Ustundag, Bilal; Ozercan, Ibrahim Hanefi; Ayten, Refik; Kanat, Burhan Hakan



Oxidation of N-hydroxy-l-arginine by hypochlorous acid to form nitroxyl (HNO).  


Recent research has shown that nitroxyl (HNO) has important and unique biological activity, especially as a potential alternative to current treatments of cardiac failure. HNO is a reactive molecule that undergoes efficient dimerization and subsequent dehydration to form nitrous oxide (N(2)O), making its detection in solution or biologically relevant preparations difficult. Due to this limitation, HNO has not yet been observed in vivo, though several pathways for its endogenous generation have been postulated. Here, we investigate the oxidation of N-hydroxy-l-arginine (NOHA) by hypochlorous acid (HOCl), which is generated in vivo from hydrogen peroxide and chloride by the heme enzyme, myeloperoxidase. NOHA is an intermediate in the enzymatic production of nitric oxide (NO) by NO synthases, and has been shown previously to be chemically oxidized to either HNO or NO, depending on the oxidant employed. Using membrane inlet mass spectrometry and standard N(2)O analysis by gas chromatography, we find that NOHA is oxidized by excess HOCl to form HNO-derived N(2)O. In addition, we also observe the analogous production of HNO from the HOCl oxidation of hydroxylamine, hydroxyurea, and (to a lesser extent) acetohydroxamic acid. PMID:23102772

Cline, Meredith R; Chavez, Tyler A; Toscano, John P



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  

Microsoft Academic Search

The known effects of a novel stomach pentadecapeptide BPC157 (10 ?g 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 NG-nitro-l-arginine methylester (l-NAME) (5 mg\\/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor,

Predrag Sikiri?; Sven Seiwerth; Željko Grabarevi?; Rudolf Ru?man; Marijan Petek; Vjekoslav Jagi?; Branko Turkovi?; Ivo Rotkvi?; Stjepan Miše; Ivan Zori?i?; Paško Konjevoda; Darko Perovi?; Ljubica Jurina; Jadranka Šeparovi?; Miro Hanževa?ki; Branka Artukovi?; Mirna Bratuli?; Marina Tišljar; Miro Gjurašin; Pavao Mikli?; Dinko Stan?i?-Rokotov; Zoran Slobodnjak; Nikola Jelovac; Anton Marovi?



Effects of Long-Term Bosentan in Children With Pulmonary Arterial Hypertension  

Microsoft Academic Search

OBJECTIVES This study investigated the long-term outcome of children with pulmonary arterial hyper- tension (PAH) treated with bosentan therapy, with or without concomitant prostanoid therapy. BACKGROUND Bosentan, an oral endothelin ETA\\/ETB receptor antagonist, improves hemodynamics and exercise capacity in adults with PAH; however, limited data are available on its long-term effects in children. METHODS In this retrospective study, 86 children

Erika Berman Rosenzweig; D. Dunbar Ivy; Allison Widlitz



L-Arginine trifluoroacetate salt bridges in its solid state compound: The low-temperature three dimensional structural determination of L-arginine bis(trifluoroacetate) crystal and its vibrational spectral analysis  

NASA Astrophysics Data System (ADS)

Structural varieties of L-arginine trifluoroacetate (abbreviated as LATF) and L-arginine bis(trifluoroacetate), LABTF, in the solid state compounds were observed and analyzed by the nuclear magnetic resonance (NMR) spectroscopy. The guanidinium-carboxylate interaction plays an important role involving in the crystal structure construction. Conformational changes of L-Arg + and L-Arg 2+ cations result from the intrinsic structural difference by hydrogen bonding and electrostatic interactions. The low-temperature structure of its crystalline salt, L-arginine bis(trifluoroacetate), was determined to describe the hydrogen bonding interactions. In comparison with the crystal structure at room temperature, the low-temperature L-Arg 2+ cations present tiny conformational difference and the rotational disorder of CF 3 group disappears. FT-IR and Raman spectra were investigated and hydrogen bonding interactions were analyzed on the basis of its vibrational spectra. Results indicate that this type interaction is greatly contributive to the structural features and vibrational spectral properties.

Sun, Z. H.; Sun, W. M.; Chen, C. T.; Zhang, G. H.; Wang, X. Q.; Xu, D.



[Taiwan long-term care insurance and the evolution of long-term care in Japan].  


The proportion of elderly (65 years of age and older) in Taiwan has exceeded 10% since 2008. With more elderly, the number of patients suffering from dementia and disabilities has also been rapidly increasing. Japan also has been facing increasing demand for long-term care due to an aging society. Prior to 2000, social welfare programs in Japan, working to cope with changing needs, typically provided insufficient services, and geriatric patients were hospitalized unnecessarily, wasting medical resources and causing undue patient hardship. In response, Japan launched its long-term care insurance program in April 2000. Under the program, city, town and village-based organizations should take responsibility for providing care to the elderly in their place of residence. The program significantly improved previous financial shortfalls and long-term care supply and demand has been met by existing social welfare organization resources. In Taiwan, the provision of long-term care by county / city authorities has proven inconsistent, with performance deemed poor after its first decade of long-term care operations. Service was found to be affected by differences in available resources and insufficient long-term care administration. The cultures of Taiwan and Japan are similar. The authors visited the Japan Long-Term Care Insurance Institute in August 2009. Main issues involved in the implementation and evolution of the Japan long-term Care Insurance are reported on in this paper. We hope such may be useful information to those working to develop long-term care programs in Taiwan. PMID:20661859

Huang, Hui-Wen; Liu, Shu-Hui; Pai, Yu-Chu



[Long-term results in pediatric orthopedics].  


Whether to treat deformities in childhood or even to operate on them is a difficult decision which may affect a patient's whole life. Most important is a sound knowledge of the natural course. Many 'deformities' are just normal variants, and others improve during the growth period, but some get worse and may cause damage in later life. However the outcome of operations is not always certain. Recurrence may occur as well as overcorrection; therefore, the long-term prognosis, with or without treatment, must be the guideline for indications. If an operation is considered, timing and extent of a correction are decisive. On the grounds of long-term outcome studies, guidelines can be established for the treatment of different diseases and deformities: upper extremities [dysmelia, elbow], spine [scoliosis, Scheuermann's disease, spondylolisthesis], hip (congenital dysplasia, Perthes' disease, slipped epiphysis), knee and feet (flatfoot, pes equinovarus). PMID:7631274

Engelhardt, P



Modeling long-term collider performance  

SciTech Connect

A model for the SSC arcs is described with multipole lattice field errors agglomerated into 32 lattice points, and with first order lattice errors and modulation provided by discrete transfer elements. Numerical solutions for long term dynamic aperture studies are obtained by multipole kick-drift tracking. The CPU time required to track through one turn is minimal, and comparable to that required to implement a one-turn fifth-order Taylor series map. Comparisons with tracking results using a fine grained representation of the lattice are made, and found to be satisfactory. The effects of tune modulation are studied and can substantially degrade long-term dynamic aperture. The effects of small relativistic momentum corrections, usually neglected for the large momenta at the SSC, are shown to have negligible influence on tracking results. 5 refs., 7 figs.

Ritson, D. (Stanford Linear Accelerator Center, Menlo Park, CA (United States) Superconducting Super Collider Lab., Dallas, TX (United States))



Long-term sequelae of electrical injury  

PubMed Central

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.

Wesner, Marni L.; Hickie, John



Long term therapy of generalized anxiety disorder  

Microsoft Academic Search

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

Frédéric Rouillon



Pupil motility in long-term diabetes  

Microsoft Academic Search

Summary  Employing infrared TV-videopupillography and the open loop stimulatory technique the ability of the pupil of the eye to react to rhythmic light stimuli of increasing frequencies was studied in 15 control subjects and 14 long-term juvenile diabetics. The degree of retinopathy varied from nil to proliferative changes. The visual acuity of all subjects studied was at least 6\\/9 and there

Á. B. Hreidarsson




Microsoft Academic Search

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



Long-Term Morbidity of PCOS  

Microsoft Academic Search

Polycystic ovary syndrome, economic burden, healthcare cost, diabetes mellitus, cardiovascular disease, dyslipidemia, metabolic\\u000a syndrome, endometrial cancer The polycystic ovary syndrome (PCOS) results in a number of immediate and long-term morbidities\\u000a that are associated with a significant impact on quality of life and on economic costs. Immediate morbidities include menstrual\\u000a dysfunction and abnormal uterine bleeding, subfertility and infertility, and androgen excess-related

Ricardo Azziz


Long-Term Metabolic Complications Posttransplantation  

Microsoft Academic Search

Approximately 4,500 transplants are performed each year in the United States. Advances in organ preservation and surgical\\u000a technique and in the management of immunosuppression have significantly improved survival. Short-term survival is excellent.\\u000a As long-term survival increases, cardiovascular complications are emerging as a major cause of morbidity and mortality. Hypertension,\\u000a dyslipidemia, and diabetes mellitus all are increased in liver transplant recipients

Lisa M. Forman


Synaptic tagging and long-term potentiation  

Microsoft Academic Search

Repeated stimulation of hippocampal neurons can induce an immediate and prolonged increase in synaptic strength that is called long-term potentiation (LTP)-the primary cellular model of memory in the mammalian brain1. An early phase of LTP (lasting less than three hours) can be dissociated from late-phase LTP by using inhibitors of transcription and translation2-8. Because protein synthesis occurs mainly in the

Uwe Frey; Richard G. M. Morris



Long term consequences of early childhood malnutrition  

Microsoft Academic Search

This paper examines the impact of pre-school malnutrition on subsequent human capital formation in rural Zimbabwe using a maternal fixed effects--instrumental variables (MFE-IV) estimator with a long term panel data set. Representations of civil war and drought shocks are used to identify differences in pre-school nutritional status across siblings. Improvements in height-for-age in pre-schoolers are associated with increased height as

Harold Alderman; John Hoddinott; Bill Kinsey



Consequences of long-term hyperparathyroidism.  


We describe a young woman with long-term untreated hyperparathyroidism with a superimposed vitamin D deficiency and an extremely decreased bone mineral density that was complicated by a vertebral fracture. Despite pretreatment with intravenous pamidronate and short-term vitamin D supplementation, severe and long-standing hypocalcaemia ('hungry bone syndrome') developed after parathyroidectomy. We discuss the consequences of hyperparathyroidism, especially the effects on bone, the complications of parathyroidectomy and the possibilities of preoperative treatment with bisphosphonates. PMID:9718941

Graal, M B; Wolffenbuttel, B H



Long-term consequences of anorexia nervosa.  


Anorexia nervosa (AN) is a psychiatric disorder that occurs mainly in female adolescents and young women. The obsessive fear of weight gain, critically limited food intake and neuroendocrine aberrations characteristic of AN have both short- and long-term consequences for the reproductive, cardiovascular, gastrointestinal and skeletal systems. Neuroendocrine changes include impairment of gonadotropin releasing-hormone (GnRH) pulsatile secretion and changes in neuropeptide activity at the hypothalamic level, which cause profound hypoestrogenism. AN is related to a decrease in bone mass density, which can lead to osteopenia and osteoporosis and a significant increase in fracture risk in later life. Rates of birth complications and low birth weight may be higher in women with previous AN. The condition is associated with fertility problems, unplanned pregnancies and generally negative attitudes to pregnancy. During pregnancy, women with the condition have higher rates of hyperemesis gravidarum, anaemia and obstetric complications, as well as impaired weight gain and compromised intrauterine foetal growth. It is reported that 80% of AN patients are affected by a cardiac complications such as sinus bradycardia, a prolonged QT interval on electrocardiography, arrythmias, myocardial mass modification and hypotension. A decrease in bone mineral density (BMD) is one of the most important medical consequences of AN. Reduced BMD may subsequently lead to a three- to seven-fold increased risk of spontaneous fractures. Untreated AN is associated with a significant increase in the risk of death. Better detection and sophisticated therapy should prevent the long-term consequences of this disorder. The aims of treatment are not only recovery but also prophylaxis and relief of the long-term effects of this disorder. Further investigations of the long-term disease risk are needed. PMID:23706279

Meczekalski, Blazej; Podfigurna-Stopa, Agnieszka; Katulski, Krzysztof



Emotional behavior in long-term marriage  

Microsoft Academic Search

In exploring the emotional climate of long-term marriages, this study used an observational coding system to identify specific emotional behaviors expressed by middle-aged and older spouses during discussions of a marital problem. One hundred and fifty-six couples differing in age and marital satisfaction were studied. Emotional behaviors expressed by couples differed as a function of age, gender, and marital satisfaction.

Laura L. Carstensen; John M. Gottman; Robert W. Levenson



Long-Term Trajectories of Adolescent Recovery  

Microsoft Academic Search

\\u000a A growing literature has emerged examining long-term patterns of substance use among teens who exhibit casual and more severe\\u000a use. This work evaluates treatment outcomes for teens who have substance abuse problems and identifies important developmental\\u000a correlates of those outcomes as teens age into young adulthood. This research informs the development of valuable addiction\\u000a recovery management models and identifies some

Sandra A. Brown; Danielle E. Ramo; Kristen G. Anderson


Dietary l-arginine and ?-tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms  

Microsoft Academic Search

Vascular oxidative stress brought about by superoxide radicals and oxidized low-density lipoproteins (oxLDL) is a major factor contributing to decreased NO-dependent vasodilator function in hypercholesterolemia and atherosclerosis. We investigated whether chronic administration of l-arginine (2% in drinking water) or of ?-tocopherol (300 mg\\/day) improves endothelium-dependent vasodilator function and systemic NO production, reduces vascular oxidative stress, and reduces the progression of

Rainer H. Böger; Stefanie M. Bode-Böger; Laddaval Phivthong-ngam; Ralf P. Brandes; Edzard Schwedhelm; Andreas Mügge; Michael Böhme; Dimitrios Tsikas; Jürgen C. Frölich



Peptidase activities in rats treated chronically with N ? -nitro- l-arginine methyl ester (L-NAME)  

Microsoft Academic Search

The chronic treatment of rats with N?-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension. This inhibition of NO production results in activation of the renin-angiotensin system, with increased activity of the carboxypeptidase angiotensin I-converting enzyme (ACE). Since chronic NO inhibition increases ACE activity, we hypothesized that this inhibition could also affect the activities of

Alessandra Linardi; Patricia Costa Panunto; Emer Suavinho Ferro; Stephen Hyslop



Albumin stimulates cell growth, L-arginine transport, and metabolism to polyamines in human proximal tubular cells  

Microsoft Academic Search

Albumin stimulates cell growth, L-arginine transport, and metabolism to polyamines in human proximal tubular cells.BackgroundPure albumin stimulates proximal tubular epithelial cell (PTEC) proliferation, and may have a role in homeostasis in health, as well as in disrupted PTEC turnover in proteinuric nephropathies. We investigated a role for arginine and its metabolites, the polyamines, in this process, given the ability of

NEIL ASHMAN; Steven M. Harwood; JULIUS KIESWICH; David A. Allen; Norman B. Roberts; A. Claudio Mendes-Ribeiro; Muhammad M. Yaqoob



Effects of supplemental L-arginine on the intestinal adaptive response after massive small-bowel resection in rats  

Microsoft Academic Search

To evaluate whether L-arginine methyl ester (L-Arg) can improve the structure of the small intestine and enhance adaptation in an experimental model of short-bowel syndrome (SBS), 40 Sprague-Dawley rats were divided randomly into four groups of 10 each. In one group only a laparotomy was performed (G1). The remaining 30 rats underwent 90% small-bowel resection (SBR) and formed the three

Hayrettin Öztürk; Ali Dokucu; Yusuf Ya?mur; ?brahim Sari



Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages  

Microsoft Academic Search

Recent evidence has implicated galectins and their carbo- hydrate ligands as master regulators of the inflammatory response. Galectin-1, a member of this family, has shown specific anti-inflammatory and immunoregulatory effects. To gain insight into the potential mechanisms involved in these effects, we investigated the effects of galectin-1 in L-arginine metabolism of peritoneal rat macrophages. Pre- treatment of macrophages with galectin-1

Silvia G. Correa; Claudia E. Sotomayor; Maria P. Aoki; Cristina A. Maldonado; Gabriel A. Rabinovich



Single crystal growth, crystal structure and characterization of a novel crystal: l-arginine 4-nitrophenolate 4-nitrophenol dehydrate (LAPP)  

Microsoft Academic Search

A novel organic crystal, l-arginine 4-nitrophenolate 4-nitrophenol dehydrate (LAPP), synthesized and grown from aqueous solution, is presented. X-ray single diffraction shows that LAPP belongs to the monoclinic crystallographic system with space group P21. FT-IR and UV\\/vis\\/NIR transmission spectra have been employed to characterize the crystal. The computational calculation based on the density functional theory at the B3LYP\\/6-31G (d, p) level

L. Wang; X. Q. Wang; G. H. Zhang; X. T. Liu; Z. H. Sun; G. H. Sun; W. T. Yu; D. Xu



Tandem antifibrotic actions of L-arginine supplementation and low protein diet during the repair phase of experimental glomerulonephritis  

Microsoft Academic Search

Tandem antifibrotic actions of L-arginine supplementation and low protein diet during the repair phase of experimental glomerulonephritis.BackgroundBased upon the central role transforming growth factor-beta (TGF-?) overexpression appears to play in renal fibrotic diseases, we have recently advocated reduction of TGF-? as a therapeutic target. As part of efforts to determine the strength of this approach, we have undertaken studies to

Harm Peters; Wayne A Border; Nancy A Noble



Effects of Intragastric L-Arginine Administration on Proximal Stomach Tone Under Basal Conditions and After an Intragastric Diet  

Microsoft Academic Search

Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract.\\u000a Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO,\\u000a on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly\\u000a the effect on antral

Guillaume Savoye; Yassine Jemaa; Grégory Mosni; Céline Savoye-Collet; Paola Morcamp; Pierre Déchelotte; Mickael Bouin; Philippe Denis; Philippe Ducrotté



Titanium for long-term tritium storage  

SciTech Connect

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.

Heung, L.K.



Long-term outcomes of stapled hemorrhoidopexy  

PubMed Central

Introduction Hemorrhoidal disease is one of the commonest anorectal disorders worldwide. Stapled hemorrhoidopexy (SH) is a treatment modality associated with low postoperative pain and early mobilization. Aim To assess long-term outcomes after SH. Material and methods All 326 patients who underwent SH in 1999–2003 were invited by mail to participate. For each patient we analyzed their medical records, and conducted a questionnaire survey and a digital rectal examination. Results Only 91 patients attended the final examination and the mean ± SD follow-up time was 8.7 ±1.2 years. Recurrences were diagnosed in one third of the 91 subjects. There were correlations between recurrences and: the duration of disease (p = 0.047); female gender (p = 0.037); and childbirth (vaginal delivery) (p = 0.026). Sixty-seven patients (73.6%) were satisfied with the outcomes. In the group of dissatisfied patients symptoms such as pain (p = 0.0001), burning (p = 0.0002) and itching (p = 0.014) were most common. Long-term outcomes were good with 75% and 88% reductions in pain sensation and severe and moderate hemorrhoidal bleeding. Pruritus, burning and discomfort resolved in more than 50% of patients. Flatus incontinence, fecal incontinence, or soiling occurred in 21%, 11%, and 32% of patients. Conclusions Long-term results of stapled hemorrhoidopexy are satisfactory in most patients. The 36% recurrence rate correlates with the degree of hemorrhoidal prolapse before the operation, duration of the disease, female gender, and previous vaginal delivery.

Michalik, Maciej; Bobowicz, Maciej; Witzling, Mieczyslaw



Infective endocarditis: determinants of long term outcome  

PubMed Central

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.

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



Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction.  


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 ?-glutamyl transpeptidase (?-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. PMID:21618639

Aoki, Hiromitsu; Nagao, Junji; Ueda, Taro; Strong, Jeffry M; Schonlau, Frank; Yu-Jing, Song; Lu, Yan; Horie, Shigeo



Enhanced production of L-arginine by expression of Vitreoscilla hemoglobin using a novel expression system in Corynebacterium crenatum.  


Corynebacterium crenatum SYPA 5-5 is an aerobic and industrial L: -arginine producer. It was proved that the Corynebacterium glutamicum/Escherichia coli shuttle vector pJC1 could be extended in C. crenatum efficiently when using the chloramphenicol acetyltransferase gene (cat) as a reporter under the control of promoter tac. The expression system was applied to over-express the gene vgb coding Vitreoscilla hemoglobin (VHb) to further increase the dissolved oxygen in C. crenatum. As a result, the recombinant C. crenatum containing the pJC-tac-vgb plasmid expressed VHb at a level of 3.4 nmol?g(-1), and the oxygen uptake rates reached 0.25 mg A(562)(-1) ?h(-1) which enhanced 38.8% compared to the wild-type strain. Thus, the final L: -arginine concentration of the batch fermentation reached a high level of 35.9 g?L(-1), and the biomass was largely increased to 6.45 g?L(-1), which were 17.3% and 10.5% higher than those obtained by the wild-type strain, respectively. To our knowledge, this is the first report that the efficient expression system was constructed to introduce vgb gene increasing the oxygen and energy supply for L: -arginine production in C. crenatum, which supplies a good strategy for the improvement of amino acid products. PMID:20835781

Xu, Meijuan; Rao, Zhiming; Xu, Hong; Lan, Chunyan; Dou, Wenfang; Zhang, Xiaomei; Xu, Hongyu; Jin, Jian; Xu, Zhenghong



Galactosyl derivative of N(omega)-nitro-L-arginine: study of antiproliferative activity on human thyroid follicular carcinoma cells.  


The methyl ester prodrug of N(omega)-nitro-L-arginine (L-NAME) has been reported to exert anticancer effects against several human tumors, including thyroid carcinoma, by inhibiting nitric oxide synthase (NOS). However, chronic administration of L-NAME has often led to adverse events causing cardiovascular alterations due to its potential toxic effect. Here we report for the first time the synthesis of the galactosyl ester prodrug of N(omega)-nitro-L-arginine, NAGAL, a prodrug capable of inhibiting NOS more efficiently and with fewer adverse events than its parent drug. For this purpose RO82-W-1, a thyroid cell line derived from human follicular carcinoma, was used. MTT test results showed that NAGAL affected cell viability to a significantly greater extent than did L-NAME. Moreover, fluorescence activated cell sorter (FACS) analyses revealed that NAGAL, compared to L-NAME, was able to reduce nitric oxide (NO) production as well as increase the percentage of apoptotic thyreocytes. Western blot further confirmed the reduction in NOS-II expression by NAGAL. Finally, by using the LC-MS technique, we found that NAGAL elicited a higher increase in N(omega)-nitro-L-arginine (NA) concentration than did L-NAME. Thus, this study suggests that NAGAL could be considered a potential therapeutic tool for those pathologies involving an overproduction of NO, including thyroid carcinoma. PMID:19650107

Melisi, Daniela; Rosso, Francesco; Curcio, Annalisa; Tortora, Carla; Nieddu, Maria; Marino, Gerardo; Lettieri, Maria; Grimaldi, Anna; Luongo, Elvira; Romano, Simona; Romano, Maria Fiammetta; Boatto, Gianpiero; Abignente, Enrico; Barbarisi, Alfonso; Rimoli, Maria Grazia



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


A novel L-arginine-selective amperometric bi-enzyme biosensor based on recombinant human arginase I isolated from the gene-engineered strain of methylotrophic yeast Hansenula polymorpha and commercial urease is described. The biosensing layer was placed onto a polyaniline-Nafion composite platinum electrode and covered with a calcium alginate gel. The developed sensor revealed a good selectivity to L-arginine. The sensitivity of the biosensor was 110 ± 1.3 nA/(mM mm(2)) with the apparent Michaelis-Menten constant (K(M)(app)) derived from an L-arginine (L-Arg) calibration curve of 1.27 ± 0.29 mM. A linear concentration range was observed from 0.07 to 0.6mM, a limit of detection being 0.038 mM and a response time - 10s. The developed biosensor demonstrated good storage stability. A laboratory prototype of the proposed amperometric biosensor was applied to the samples of three commercial pharmaceuticals ("Tivortin", "Cytrarginine", "Aminoplazmal 10% E") for L-Arg testing. The obtained L-Arg-content values correlated well with those declared by producers. PMID:22626826

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



Links between short and long term tectonics  

NASA Astrophysics Data System (ADS)

In the quest for understanding the rheology of the lithosphere a central question that can be addressed is the existence of a parameterisation of the rheology, which could reflect both the response of the lithosphere over the large time scale (10's Myr) and the time scale of earthquakes and faulting. The gap existing between these observational time scales is mainly due to modelling approximations which in each separate fields permit to fit the data but which rely on simplification of the physics, the rheology and set of boundary conditions which are not always compatible one with each other. The long-term community, i.e. the geodynamics community, tend to use Mohr-Coulomb non-associated plasticity to model self-consistent shear zone localisation. This type of rheology corresponds, in the limit of a discrete fault plan, to a slip weakening/hardening formulation in which weakening rate depends on fault plan orientation. The short term community, i.e. the earthquake community, has stopped using this kind of formulation and rather uses the rate and state formulation to model the activity of faults. Rate and State is limited because it cannot self-consistently generate an earthquake, the triggering, i.e. the initial slip acceleration must be imposed. This contribution is a synthesis of several geological case studies at different length-scale, in which we suspects a strong link between long term geodynamic processes and current seismological and geodetic observations. We make use of these case studies together with quantitative numerical models to understand how the seismic and inter-seismic behaviour reflects the rather long-term geodynamic setting than the internal rheological properties of faults. After briefly revisiting the different modelling approaches from geodynamic seismologic and geodetic communities, we show how modelling results obtained with the long term modelling approach brings new insights and alternative models for both the seismological and geodetic behaviour of active faults. The first example will concern the seismic activity on low angle normal faults focussing on the case of the Gulf of Corinth. Then focusing on strike slip tectonic, I will compare data from active and exhumed strike slip faults and discuss how a single model can explain their behaviour. The last example will focus on the creeping segment of the San Andreas Fault to discuss how heterogeneities in the long-term tectonic loading (in that instance flexure of the lithosphere) may influence the seismic behaviour of strike slip fault.

Le Pourhiet, Laetitia; Traoré, Nafissatou; Lecomte, Emmanuel; Saleeby, Jason



125I-8-L-arginine vasopressin binding to human mononuclear phagocytes.  

PubMed Central

The binding of vasopressin to human circulating blood cells was examined. Direct binding studies with preparations of single cell types indicated that the mononuclear phagocyte system is almost entirely responsible for binding of the hormone. Binding of 125I-8-L-arginine vasopressin (AVP) (40 pM) in the presence of excess unlabeled hormone was saturable (2.8 +/- 0.4 fmol/2 x 10(6) cells per ml), was linear with cell number, was dependent upon the concentration of the radioligand used, and was reversible. Binding equilibrium was achieved in 30--40 min at 22 degrees C. Scatchard analysis of binding at this time showed an apparent dissociation constant of 25 +/- 0.21 pM, providing an estimate of 640 +/- 80 sites/cell. Pretreatment of the cells with cytochalasin B, an agent that can block phagocytosis, did not modify radioligand binding, which indicates that 125I-AVP uptake by the cells is due to binding and not to endocytosis. Specificity of vasopressin-sensitive sites on mononuclear phagocytes was demonstrated with a series of vasopressin analogues with various degrees of antidiuretic potency, and with peptide hormones that bind to specific receptors on circulating blood cells but that lack antidiuretic activity. AVP (40 pM) elevated the intracellular level of cyclic AMP from 137 +/- 8.6 to 350 +/- 20.5 pmol/mg cell protein. The binding affinities of the various analogues were correlated with their ability to stimulate intracellular cyclic AMP synthesis (Lys8-vasopressin less than deamino(8-D-Arg)-vasopressin less than oxytocin).

Block, L H; Locher, R; Tenschert, W; Siegenthaler, W; Hofmann, T; Mettler, E; Vetter, W



Increased Serum Levels of L-Arginine in Ulcerative Colitis and Correlation with Disease Severity  

PubMed Central

Background L-arginine (L-Arg) is a semi-essential amino acid that is the substrate for both nitric oxide and polyamine synthesis. Cellular uptake of L-Arg is an active transport process that is subject to competitive inhibition by L-ornithine (L-Orn) and L-lysine (L-Lys). We investigated L-Arg utilization in patients with ulcerative colitis (UC). Methods Serum was collected from 14 normal controls and 22 UC patients with pancolitis of moderate or severe activity by histopathology score. The Mayo Disease Activity Index (DAI) and endoscopy sub-score were assessed. Serum amino acid levels were measured by high performance liquid chromatography. Arginine availability index (AAI) was defined as [L-Arg]/([L-Orn] + [L-Lys]). Results Serum L-Arg levels were significantly associated with histopathologic grade (P = 0.001). L-Arg levels were increased in subjects with severe colitis when compared to those with moderate colitis or normal mucosa. L-Orn + L-Lys levels were also increased in severe colitis, so that AAI was not significantly increased. L-Arg levels were also strongly associated with the endoscopy sub-score (P < 0.001). There was a strong correlation between DAI and L-Arg levels (r = 0.656, P < 0.001). Conclusions Serum L-Arg levels correlate with UC disease severity, but availability is not increased, due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options.

Hong, Shih-Kuang S.; Maltz, Brad E.; Coburn, Lori A.; Slaughter, James C.; Chaturvedi, Rupesh; Schwartz, David A.; Wilson, Keith T.



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

PubMed Central

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 ?mol 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.

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



N omega-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs.  


The mechanism by which halothane, isoflurane, and nitrous oxide increase cerebral blood flow (CBF) is unknown. We assessed the cerebrovascular effects of nitrous oxide (70%; n = 6), isoflurane (1 minimum alveolar anesthetic concentration: 1.4%; n = 6) or halothane (1 minimum alveolar anesthetic concentration: 0.8%; n = 6) before and after blockade of nitric oxide (NO) synthase with 40 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously in dogs with baseline pentobarbital anesthesia. Baseline CBF (microspheres) was determined after 1 h of pentobarbital anesthesia. Cerebral perfusion pressure (CPP) was maintained during inhaled anesthetic or L-NAME by either hemorrhage or inflation of an intra-aortic balloon. Before L-NAME, halothane and isoflurane increased CBF (40 +/- 4 to 56 +/- 6 mL.min-1 x 100 g-1 and 43 +/- 6 to 78 +/- 12 mL.min-1 x 100 g-1, respectively) with no change in cerebral oxygen consumption (baseline: halothane, 2.6 +/- 0.2; isoflurane, 2.0 +/- 0.2 mL.min-1 x 100 g-1). On the contrary, nitrous oxide increased CBF similarly (40 +/- 6 to 57 +/- 8 mL.min-1 x 100 g-1), but increased cerebral oxygen consumption (2.2 +/- 0.3 to 3.0 +/- 0.3 mL.min-1 x 100 g-1). L-NAME decreased blood flow in the neurohypophysis by 80% with no change in blood flow in other brain regions. After L-NAME, reexposure to nitrous oxide, halothane, or isoflurane resulted in no change in CBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8214724

McPherson, R W; Kirsch, J R; Moore, L E; Traystman, R J



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

SciTech Connect

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.

Chen, Han; Sun, Yan Ping; Li, Yang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)] [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Liu, Wen Wu [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China)] [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xiang, Hong Gang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)] [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Fan, Lie Ying [Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai 200120 (China)] [Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai 200120 (China); Sun, Qiang [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China)] [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xu, Xin Yun [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)] [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Cai, Jian Mei [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China)] [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Ruan, Can Ping; Su, Ning; Yan, Rong Lin [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)] [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Sun, Xue Jun, E-mail: [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Wang, Qiang, E-mail: [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)] [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)



A theoretical investigation of electric properties of L-arginine phosphate monohydrate including environment polarization effects  

NASA Astrophysics Data System (ADS)

The dipole moment (?), linear polarizability (?), and first hyperpolarizability (?tot) of the asymmetric unit of L-arginine phosphate (LAP) monohydrate crystal are investigated using the supermolecule approach in combination with an iterative electrostatic polarization scheme. Environment polarization effects are attained by assuring the convergence of the dipole moment of LAP embedded in the polarization field of the surrounding molecules whose atomic sites are treated as point charges. The results obtained show that in the presence of the embedding charges, the value of ? is increased by 9% but the static values of ? and ?tot are decreased, respectively, by 3% and 13%, as compared with the isolated situation. The MP2/6-311+G(d) model predicts for the in-crystal dipole moment the converged value of 33 D, in good concordance with the available experimental result of 32 D. Our estimates for the converged results of ? and ?tot are, respectively, 22.51×10-24 and 5.01×10-30 esu. Dispersion effects are found to have a small impact on the nonlinear optical responses of LAP in the visible region. In addition, MP2/6-311G results obtained for ?tot by using isolated and embedded LAP dimers show that crystal packing effects have a significant contribution of the electrostatic interactions. Our results suggest that the role of the crystal environment is to minimize the effects of the intermolecular interactions in the electric properties. That is, ? and ?tot gain a more additive character in the presence of the field of the embedding charges. This is specially marked for ?tot.

Fonseca, T. L.; Sabino, J. R.; Castro, M. A.; Georg, H. C.



L-Arginine infusion during resuscitation for hemorrhagic shock: Impact and mechanism  

PubMed Central

BACKGROUND Our previous work showed a survival advantage with L-arginine (L-Arg) pretreatment in a swine model of severe hemorrhagic shock. This study was designed to evaluating whether the benefit is sustained when L-Arg is given during resuscitation and whether the mechanism is mediated by enzymatic activation of nitric oxide (NO) synthesis. METHODS Adult rats (n =30) underwent 40% blood volume loss and were resuscitated with saline (3×shed blood volume). Animals were divided into five treatment groups of six animals each: (1) Sham, (2) Control (resuscitation alone), (3) L-Arg (300 mg/kg) with resuscitation, (4) L-Arg +L-nitroarginine methyl ester pretreatment, and (5) D-arginine (300 mg/kg) with resuscitation. Animals were observed for 240 minutes postresuscitation or until death. Hemodynamic, metabolic, histologic, and survival outcomes were measured. RESULTS Administration of L-Arg after hemorrhage and before resuscitation significantly improved outcomes, relative to the control group. The L-Arg infusion improved terminal arterial pressures, lowered lactate, improved small bowel histologic signs of reperfusion injury, and increased survival (p <0.05). Endpoints of the L-Arg group were similar to the Sham group. The benefits of L-Arg infusion were abolished or attenuated when animals were pretreated with L-nitroarginine methyl ester and potentiated with D-arginine, suggesting a NO-specific mechanism of L-Arg. Finally, severe shock and resuscitation injury significantly elevated circulating asymmetric dimethylarginine levels, which are potent competitive inhibitors of NO synthetase. CONCLUSION L-Arg infusion during resuscitation offers a significant functional, metabolic, and survival benefit after severe hemorrhagic shock. The mechanism seems to be by activation of NO synthesis with its attendant benefits to local perfusion and inflammation after global reperfusion.

Arora, Tania K.; Malhotra, Ajai K.; Ivatury, Rao; Mangino, Martin J.



L-arginine Supplementation Improves Responses to Injury and Inflammation in Dextran Sulfate Sodium Colitis  

PubMed Central

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

Coburn, Lori A.; Gong, Xue; Singh, Kshipra; Asim, Mohammad; Scull, Brooks P.; Allaman, Margaret M.; Williams, Christopher S.; Rosen, Michael J.; Washington, M. Kay; Barry, Daniel P.; Piazuelo, M. Blanca; Casero, Robert A.; Chaturvedi, Rupesh; Zhao, Zhongming; Wilson, Keith T.



L-lysine catabolism is controlled by L-arginine and ArgR in Pseudomonas aeruginosa PAO1.  


In comparison to other pseudomonads, Pseudomonas aeruginosa grows poorly in L-lysine as a sole source of nutrient. In this study, the ldcA gene (lysine decarboxylase A; PA1818), previously identified as a member of the ArgR regulon of L-arginine metabolism, was found essential for L-lysine catabolism in this organism. LdcA was purified to homogeneity from a recombinant strain of Escherichia coli, and the results of enzyme characterization revealed that this pyridoxal-5-phosphate-dependent decarboxylase takes L-lysine, but not L-arginine, as a substrate. At an optimal pH of 8.5, cooperative substrate activation by L-lysine was depicted from kinetics studies, with calculated K(m) and V(max) values of 0.73 mM and 2.2 ?mole/mg/min, respectively. Contrarily, the ldcA promoter was induced by exogenous L-arginine but not by L-lysine in the wild-type strain PAO1, and the binding of ArgR to this promoter region was demonstrated by electromobility shift assays. This peculiar arginine control on lysine utilization was also noted from uptake experiments in which incorporation of radioactively labeled L-lysine was enhanced in cells grown in the presence of L-arginine but not L-lysine. Rapid growth on L-lysine was detected in a mutant devoid of the main arginine catabolic pathway and with a higher basal level of the intracellular L-arginine pool and hence elevated ArgR-responsive regulons, including ldcA. Growth on L-lysine as a nitrogen source can also be enhanced when the aruH gene encoding an arginine/lysine:pyruvate transaminase was expressed constitutively from plasmids; however, no growth of the ldcA mutant on L-lysine suggests a minor role of this transaminase in L-lysine catabolism. In summary, this study reveals a tight connection of lysine catabolism to the arginine regulatory network, and the lack of lysine-responsive control on lysine uptake and decarboxylation provides an explanation of L-lysine as a poor nutrient for P. aeruginosa. PMID:20833801

Chou, Han Ting; Hegazy, Mohamed; Lu, Chung-Dar



The effects of L-arginine and L-NAME supplementation on redox-regulation and thermogenesis in interscapular brown adipose tissue  

Microsoft Academic Search

Changes in inducible nitric oxide synthase (iNOS) protein levels and its relationship with the hyperplasia and uncoupling protein 1 (UCP1) levels were examined in interscapular brown adipose tissue (IBAT) of adult rat males receiving L-arginine (L-Arg; 2.25%) or N-nitro-L- arginine methyl ester (L-NAME; 0.01%) as a drinking liquid and maintained at low (4±1°C) or room (22±1°C) temperature for 45 days.

Vesna Petrovic; Aleksandra Korac; Biljana Buzadzic; Bato Korac; Sinisa Stankovic; Bulevar Despota



Restoring vascular nitric oxide formation by l-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease  

Microsoft Academic Search

Background. Administration of l-arginine improves nitric oxide (NO) formation and endothelium-dependent vasodilation in atherosclerotic patients.Objectives. We investigated in this double-blind, controlled study whether prolonged intermittent infusion therapy with l-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium-independent vasodilator prostaglandin E1, and control patients.Methods. Thirty-nine patients with intermittent claudication were randomly assigned to receive 2

Rainer H Böger; Stefanie M Bode-Böger; Wolfgang Thiele; Andreas Creutzig; Klaus Alexander; Jürgen C Frölich



Effect of Native and Oxidized Low-Density Lipoprotein on Endothelial Nitric Oxide and Superoxide Production Key Role of L-Arginine Availability  

Microsoft Academic Search

lipoprotein concentrations on endothelial NO and superoxide (O22) production. We investigated where lipoproteins may affect the L-arginine-NO pathway by pretreating cells with L-arginine, L-N-arginine methyl ester (L-NAME), and superoxide dismutase. Bovine aortic endothelial cells were exposed for 1 hour to increasing concentrations of n-LDL (from 0 to 240 mg cholesterol\\/dL) and ox-LDL (from 0 to 140 mg cholesterol\\/dL). A stimulated

Luciana Vergnani; Stefan Hatrik; Franco Ricci; Angelina Passaro; Nadia Manzoli; Giovanni Zuliani; Viktor Brovkovych; Renato Fellin; Tadeusz Malinski


Long-term administration of beraprost sodium for pulmonary arterial hypertension associated with congenital heart disease.  


Pulmonary arterial hypertension (PAH) is often associated with congenital heart disease (CHD). Acute administration of beraprost reduces pulmonary vascular resistance in patients with idiopathic PAH and PAH associated with CHD; however, little is known about whether or not long-term treatment with oral beraprost benefits these patients. We report the case of a patient suffering from severe PAH associated with large patent ductus arteriosus (PDA), who was considered to be ineligible for PDA closure using a conventional treatment strategy. Eventually, long-term administration of oral beraprost ameliorated the degree of PAH and the patient subsequently underwent successful closure of the PDA. PMID:19721298

Oyamada, Jun; Toyono, Manatomo; Shimada, Shunsuke; Aoki-Okazaki, Mieko; Tamura, Masamichi; Takahashi, Tsutomu



Long term thermoelectric module testing system  

NASA Astrophysics Data System (ADS)

Thermoelectric generators can be used for converting waste heat into electric power. Significant interest in developing new materials in recent years has led to the discovery of several promising thermoelectrics, however, there can be considerable challenges in developing the materials into working devices. Testing and feedback is needed at each step to gain valuable information for identification of difficulties, quality of the materials and modules, repeatability in fabrication, and longevity of the devices. This paper describes a long-term module testing system for monitoring the output power of a module over extended testing times. To evaluate the system, we have tested commercially available thermoelectric modules over a one month time period.

D'Angelo, Jonathan; Hogan, Timothy



Long-term space flights - personal impressions  

NASA Astrophysics Data System (ADS)

During a final 4-month stage of a 1-year space flight of cosmonauts Titov and Manarov, a physician, Valery Polyakov was included on a crew for the purpose of evaluating their health, correcting physical status to prepare for the spacecraft reentry and landing operations. The complex program of scientific investigations and experiments performed by the physician included an evaluation of adaptation reactions of the human body at different stages of space mission using clinicophysiological and biochemical methods; testing of alternative regimes of exercise and new countermeasures to prevent an unfavourable effect of long-term weightlessness.

Polyakov, V. V.


Dacryocystostenting: technical and long-term results  

Microsoft Academic Search

Purpose.  We describe our experience in treating epiphora caused by chronic inflammation and obstruction of the nasolacrimal system\\u000a by endonasal placement of a polyurethane stent in the nasolacrimal duct, with long-term assessment of patency (4 years).\\u000a \\u000a \\u000a \\u000a Material and methods.  Between July 1998 and May 2001, 57 stents were inserted using Song’s technique. All procedures were carried out in the radiology\\u000a suite following

P. Falappa; M. Ortenzi; F. Passarelli; M. Micozzi



Long-Term Wind Power Variability  

SciTech Connect

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.

Wan, Y. H.



[Long term prognosis after circulatory arrest].  


24 PATIENTS HAVING SURVIVED MORE THAN 18 MONTHS AFTER AN EPISODE OF CIRCULATORY ARREST WERE EXAMINED WITH THE AIM OF ASSESSING THE PSYCHOLOGICAL REACTIONS TO SUCH AN INCIDENT. The results obtained were encouraging, since immediately after the circulatory arrest there were only monor troubles reflecting the simple bringing into action of defence mechanisms. Long term adaptation was deemed excellent in 80 p.cent of cases which should, nevertheless, lead to any underestimation of those sequelae which, though happily rare, are highly incapacitating. PMID:1153308

Nicolas, G; Besancon, G; Bouhour, J B; Godin, J F; Vincent, J P



Performance considerations in long-term spaceflight  

NASA Technical Reports Server (NTRS)

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.

Akins, F. R.



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

PubMed Central

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.

Sugimoto, Y; Toyoshima, S



The influence of short-term L-arginine supplementation on rats' muscular and hepatic cells in ischemia-reperfusion syndrome.  


Due to the complex mechanisms of L-arginine activity, it is difficult to determine the clinical significance of supplementation with this amino acid. The objective of this study was to determine the influence of short-term supplementation with L-arginine in stress conditions, induced by ischemia-reperfusion syndrome, by assessing the damage to muscular and hepatic cells on the basis of creatine kinase (CK), alanine aminotransferase (ALAT) and aspartic aminotransferase (AspAT) activity in blood and the level of oxygen free radicals in analyzed tissues of rats. We observed that induced ischemia of hind limb caused an increase in CK, ALAT and AspAT activity and an increase in the level of free radicals in liver, but not in skeletal muscle. Supplementation with L-arginine led to a reduction in serum activity of CK and AspAT and reduction of the level of free radicals in analysed tissues. Simultaneous supplementation with L -arginine AND L-NAME resulted in a reversal of changes induced by L-arginine supplementation in the case of AspAT and free radicals in skeletal muscle. The results indicate that under conditions of ischemia-reperfusion, short-term administration of L-arginine has a protective effect on skeletal muscle manifesting itself by reduction of CK in the serum and reduction of free radicals level in THIS tissue. PMID:21948185

Sosnowski, Przemys?aw; Krauss, Hanna; Bogdanski, Pawel; Suliburska, Joanna; Jablecka, Anna; Cieslewicz, Artur; Pupek-Musialik, Danuta; Jastak, Rafa?



N sup G -methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: Implications for the involvement of nitric oxide  

SciTech Connect

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 N{sup G}-methyl-L-arginine. The authors found that hypotension induced in pentobarbital-anesthetized dogs by TNF was completely reversed within 2 min following administration of N{sup G}-methyl-L-arginine. In contrast, N{sup G}-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 monenzymatic, arginine-independent mechanism. The effect of N{sup G}-methyl-L-arginine on TNF-induced hypotension was antagonized, and the hypotension restored, by administration of excess L-arginine findings suggest that excessive nitric oxide production mediates the hypotensive effect of TNF.

Kilbourn, R.G.; Adams, J. (Univ. of Texas M. D. Anderson Cancer Center, Houston (USA)); Gross, S.S.; Griffith, O.W.; Levi, R. (Cornell Univ. Medical College, New York, NY (USA)); Jubran, A.; Lodato, R.F. (Univ. of Texas Health Science Center, Houston (USA))



Oral Contraceptives Reduce Long-Term Risk of Ovarian Cancer

Since they were first licensed nearly 50 years ago, birth control pills containing estrogen have prevented some 200,000 cases of ovarian cancer world-wide, estimate the authors of a study published January 26, 2008, in The Lancet.


Clinical review: Long-term noninvasive ventilation  

PubMed Central

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.

Robert, Dominique; Argaud, Laurent



The Long-Term Hemispheric Sunspot Activity  

NASA Astrophysics Data System (ADS)

Sunspot activity is usually represented by either sunspot numbers (SN) or sunspot areas (SA). The smoothed monthly mean SA and SN in the northern and southern hemispheres from 1945 January to 2008 March are used to investigate the characteristics of long-term hemispheric sunspot activity. Although sunspot activity (SA and SN) is found to begin one month earlier in the northern hemisphere than in the southern hemisphere on the average of the considered time interval, the shift is so small that no long-term systematic phase shift is statistically acceptable as a first-order effect, as suggested by White & Trotter. Sunspot activity never peaks at the same time in the two hemispheres. Although the Schwabe cycle appears in hemispheric sunspot activity, its period length slightly varies during the considered time interval and seems to be longer in the southern hemisphere than in the northern hemisphere on the average. Sunspot activity is asymmetrically distributed in the hemispheres, but the largest hemispheric diversity usually does not appear around the maximum time of a cycle. The diversity of SA, respectively, in the northern and southern hemispheres runs on the Sun similarly and synchronously as the diversity of SN does. Sunspot activity is slightly asynchronous in the hemispheres.

Li, K. J.; Gao, P. X.; Zhan, L. S.; Shi, X. J.



Toward a comprehensive long term nicotine policy  

PubMed Central

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

Gray, N; Henningfield, J; Benowitz, N; Connolly, G; Dresler, C; Fagerstrom, K; Jarvis, M; Boyle, P



Long term effects of Escherichia coli mastitis.  


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 1500?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. PMID:24906501

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



Sleep facilitates long-term face adaptation.  


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

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



Sleep facilitates long-term face adaptation  

PubMed Central

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.

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



Long-term intracranial pressure monitoring.  


Continuous or intermittent measurement of intracranial pressure (ICP) is important in patients at risk for raised ICP. Indications exist for short- and long-term measurements. The various methods used for short-term monitoring are discussed with their relative advantages and disadvantages. For long-term measurements of ICP use of a completely implantable telemetric epidural pressure transducer is indicated. No such device is commercially available. We have developed an inexpensive passive telemetric transducer for this purpose. Results obtained up till now have demonstrated its reliability for measurements of two to three months duration. The life span of the device is limited by degrading of the epoxy utilized for sealing of the titanium pressure sensing part to the radiolucent ceramic cap of the transducer, causing leakage of water into the transducer and false low measurements. Because of these problems new hermetic sealing techniques were tested. Both active metal brazing and glass bonding yielded good results and hermetic sealing could be obtained. The metal to ceramic bonding presented is generally applicable within the design of implants. Besides the technical progress reported, the experience with clinical use in 12 patients is presented. PMID:6674738

de Jong, D A; Maas, A I; den Ouden, A H; de Lange, S A


Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats  

PubMed Central

AIM: To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats. METHODS: Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2 g/kg body weight L-Arg i.p. at an interval of 1 h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1 h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection. RESULTS: L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes. CONCLUSION: Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.

Szabolcs, Annamaria; Reiter, Russel J; Letoha, Tamas; Hegyi, Peter; Papai, Gabor; Varga, Ilona; Jarmay, Katalin; Kaszaki, Jozsef; Sari, Reka; Jr, Zoltan Rakonczay; Lonovics, Janos; Takacs, Tamas



Long-term management of gastroesophageal reflux disease with pantoprazole  

PubMed Central

Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease that can progress to major complications. Affected patients have poorer health-related quality of life than the general population. As GERD requires continued therapy to prevent relapse and complications, most patients with erosive esophagitis require long-term acid suppressive treatment. Thus GERD results in a significant cost burden and poor health-related quality of life. The effective treatment of GERD provides symptom resolution and high rates of remission in erosive esophagitis, lowers the incidence of GERD complications, improves health-related quality of life, and reduces the cost of this disease. Proton pump inhibitors are accepted as the most effective initial and maintenance treatment for GERD. Oral pantoprazole is a safe, well tolerated and effective initial and maintenance treatment for patients with nonerosive GERD or erosive esophagitis. Oral pantoprazole has greater efficacy than histamine H2-receptor antagonists and generally similar efficacy to other proton pump inhibitors for the initial and maintenance treatment of GERD. In addition, oral pantoprazole has been shown to improve the quality of life of patients with GERD and is associated with high levels of patient satisfaction with therapy. GERD appears to be more common and more severe in the elderly, and pantoprazole has shown to be an effective treatment for this at-risk population.

Scholten, Theo



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

SciTech Connect

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 and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be used as a potential treatment method to alleviate the late diabetic complications.

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



Advanced long term cryogenic storage systems  

NASA Technical Reports Server (NTRS)

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.

Brown, Norman S.



Long term cryogenic storage facility systems study  

NASA Technical Reports Server (NTRS)

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.

Schuster, John R.



Safety of long-term PPI therapy.  


Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been published in the past decade and are critically reviewed in this article and the existing evidence is evaluated and translated into possible clinical consequences. Based on the existing evidence the benefits of PPI treatment seem to outweigh potential risks in the large majority of patients especially if PPI use is based on a relevant indication. The concern for complications should primarily be directed at elderly, malnourished with significant co-morbidity. In this population an increased risk for enteric infections, fractures and nutritional deficiencies might have clinical consequences and should lead to a careful evaluation of the indication for PPI treatment. PMID:23998981

Reimer, Christina



Long-term U. S. energy outlook  

SciTech Connect

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.

Friesen, G.



Reducing long-term reservoir performance uncertainty  

SciTech Connect

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.

Lippmann, M.J.



Gazprom outlines long term Soviet gas plan  

SciTech Connect

This paper reports that the U.S.S.R.'s Gazprom Konstern has drawn up a comprehensive, long term plan for the Soviet natural gas industry, Eastern Bloc Energy (EBE) reports. EBE is a publication of Eastern Bloc Research Ltd., Newton Kyme, England. Gazprom, responsible for more than 90% of Soviet gas production, predicts Soviet gas production will continue to increase beyond 2030 and expects the resource base ultimately will total more than 330 trillion cu m, EBE the. Soviet Central Asia will begin to decline as a major source of gas during the early years of the next century, but western Siberian production will continue to grow after 2030. The continental shelf, mainly the Barents Sea, will eventually become a very large supplier of gas, EBE reported. Gazprom the development potential of the Soviet gas industry is not constrained by geological factors, only by economic and technical problems.

Not Available



Withdrawal from long-term benzodiazepine treatment.  

PubMed Central

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.

Petursson, H; Lader, M H



Long-term thalidomide for actinic prurigo.  


A 35-year-old man presented at the age of 8 years with recurrent pruritic papulovesicular lesions on his face and body appearing within minutes of light exposure. A recent positive finding of human leukocyte antigen (HLA) DR4 with the rare DRB1*0407 subtype confirmed a diagnosis of actinic prurigo. Thalidomide (100 mg/day) was commenced at the age of 11 years after an unsuccessful trial of other treatments and his lesions resolved within 2 months. Attempts to withdraw thalidomide have resulted in recurrence of photosensitivity and the patient has remained on a virtually continuous maintenance dose of thalidomide (50 mg/ day) for 23 years. His cumulative dose is estimated to be over 400 g. To date, he has not experienced any adverse effects and investigations have shown no evidence of neuropathy. This case illustrates the safe long-term use of thalidomide. PMID:11903163

Yong-Gee, S A; Muir, J B



Posterior urethral valves: long-term outcome.  


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. PMID:21748651

Caione, Paolo; Nappo, Simona Gerocarni



Dynamics of long-term genomic selection  

PubMed Central

Background Simulation and empirical studies of genomic selection (GS) show accuracies sufficient to generate rapid gains in early selection cycles. Beyond those cycles, allele frequency changes, recombination, and inbreeding make analytical prediction of gain impossible. The impacts of GS on long-term gain should be studied prior to its implementation. Methods A simulation case-study of this issue was done for barley, an inbred crop. On the basis of marker data on 192 breeding lines from an elite six-row spring barley program, stochastic simulation was used to explore the effects of large or small initial training populations with heritabilities of 0.2 or 0.5, applying GS before or after phenotyping, and applying additional weight on low-frequency favorable marker alleles. Genomic predictions were from ridge regression or a Bayesian analysis. Results Assuming that applying GS prior to phenotyping shortened breeding cycle time by 50%, this practice strongly increased early selection gains but also caused the loss of many favorable QTL alleles, leading to loss of genetic variance, loss of GS accuracy, and a low selection plateau. Placing additional weight on low-frequency favorable marker alleles, however, allowed GS to increase their frequency earlier on, causing an initial increase in genetic variance. This dynamic led to higher long-term gain while mitigating losses in short-term gain. Weighted GS also increased the maintenance of marker polymorphism, ensuring that QTL-marker linkage disequilibrium was higher than in unweighted GS. Conclusions Losing favorable alleles that are in weak linkage disequilibrium with markers is perhaps inevitable when using GS. Placing additional weight on low-frequency favorable alleles, however, may reduce the rate of loss of such alleles to below that of phenotypic selection. Applying such weights at the beginning of GS implementation is important.



[Primary hyperparathyroidism: postoperative long-term evolution].  


The long-term postoperative outcome of 87 patients with primary hyperparathyrodism is here presented. Of the total 78 were females and 9 males, ratio: 8.7:1. Mean age 55.3 ± 10.2 years. Before surgery, 44% had kidney stones, 70% had osteopenia or osteoporosis and 71.2% had hypercalciuria. Decrease renal glomerular filtration was found in 12.6%. Of the total, 72 patients had a single adenoma, two double adenoma, two hyperplasia, four had normal histology and seven could not dispose of the result. Serum calcium, ionized calcium, phosphorus and intact parathyroid hormone were normalized in all post surgery patients. Bone mineral density increased by 6.9% in lumbar spine and 3% in femoral neck. Markers of bone remodeling were normalized and persisted normal 23 months of follow-up, coinciding with the normal intact parathyroid hormone. Same thing happened with the values of 25 OH D. When patients whith initial hypercalciuria were compared with those with normocalciuria, no differences were found in the basal values and postsurgery in both groups. In 11 patients with previous renal glomerular filtration < 60 ml ÷ min, we found a higher intact parathyroid hormone and lower bone mineral density than the rest. The glomerular filtration rate did not change significantly after surgery. In conclusion, the surgical primary hyperparathyroidism, operated by specialized surgeons has an excellent long-term outcome, with normalization of all parameters of phosphocalcic metabolism and bone remodeling and significant improvement in bone mineral density. Adverse effects were scarce and had spontaneous resolution. PMID:20920956

Spivacow, Francisco R; Martínez, Carolina; Polonsky, Ana



[Long-term results of tricuspid prostheses].  


The results of a series of 38 patients with a tricuspid valve prostheses (:76% Starr-Edwards ball valves) associated with correction of one or two left heart valvular lesions are presented. 24 patients underwent clinical and haemodynamic assessment on average 4,2 years after surgery. The conclusions were that signs of systemic venous hypertension were mainly related to residual right ventricular failure despite normal valve function and secondarily to the poor hemodynamic profile of these prostheses and their paradoxical motion. Using these results: 18% early mortality; 24% late mortality; 24% late thrombosis amongst survivors and 52% residual right ventricular failure; and 47,5% of excellent results. The clinical and haemodynamic profiles of the patients were analysed to determine the surgical indications. Apart from the correction of associated left heart valve lesions, it seems that the prognosis in tricuspid valve repair depends on the duration of tricuspid regurgitation and the severity of right ventricular myocardial disease. In elderly patients with chronic tricuspid regurgitation and severe right ventricular failure, long-term analysis showed 87,5% poor results, whilst in younger patients with a shorter history of tricuspid regurgitation and less severe right ventricular failure, there was 77,7% excellent long-term results. Semi circular annuloplasty is widely indicated in mild or severe functional tricuspid regurgitation. Tricuspid valve replacement, a much more serious operation, remains essential in chronic organic lesions and in some cases of massive functional tricuspid regurgitation. A regards the choice of prosthesis, the authors suggest the Hancock bioprosthesis as a logical choice in cases of severe right ventricular failure as they are less prone to thrombosis than mechanical prostheses and have good haemodynamic profiles. The evolution of the right ventricular failure even after correction of tricuspid regurgitation underlines the importance of preventative therapy by early correction of left heart lesions. PMID:6794514

Ben-Ismail, M; Curran, Y; Bousnina, A



Insulin-Increased L-Arginine Transport Requires A2A Adenosine Receptors Activation in Human Umbilical Vein Endothelium  

PubMed Central

Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1). This process involves the activation of A2A adenosine receptors (A2AAR) in human umbilical vein endothelial cells (HUVECs). Insulin increases hCAT-1 activity and expression in HUVECs, and A2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C) in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor) and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR), and SLC7A1 (for hCAT-1) reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent Km for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1?1606 or pGL3-hCAT-1?650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1?1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes.

Guzman-Gutierrez, Enrique; Westermeier, Francisco; Salomon, Carlos; Gonzalez, Marcelo; Pardo, Fabian; Leiva, Andrea; Sobrevia, Luis



Effect of H + ion implantation on structural, morphological, optical and dielectric properties of L-arginine monohydrochloride monohydrate single crystals  

NASA Astrophysics Data System (ADS)

L-arginine monohydrochloride monohydrate (LAHCl) single crystals have been implanted with 100 keV H + ions at different ion fluence ranging from 10 12 to 10 15 ions/cm 2. Implanted LAHCl single crystals have been investigated for property changes. Crystal surface and crystalline perfection of the pristine and implanted crystals were analyzed by atomic force microscope and high-resolution X-ray diffraction studies, respectively. Optical absorption bands induced by colour centers, refractive index and birefringence, mechanical stability and dielectric constant of implanted crystals were studied at different ion fluence and compared with that of pristine LAHCl single crystal.

Sangeetha, K.; Babu, R. Ramesh; Kumar, P.; Bhagvannarayana, G.; Ramamurthi, K.



Single crystal growth, crystal structure and characterization of a novel crystal: L-arginine 4-nitrophenolate 4-nitrophenol dehydrate (LAPP)  

NASA Astrophysics Data System (ADS)

A novel organic crystal, L-arginine 4-nitrophenolate 4-nitrophenol dehydrate (LAPP), synthesized and grown from aqueous solution, is presented. X-ray single diffraction shows that LAPP belongs to the monoclinic crystallographic system with space group P2 1. FT-IR and UV/vis/NIR transmission spectra have been employed to characterize the crystal. The computational calculation based on the density functional theory at the B3LYP/6-31G (d, p) level has been used to compute the first-order hyperpolarizability of LAPP relating to different molecular models. The morphology, nonlinear characteristic and thermal stability of the crystal have also been investigated.

Wang, L. N.; Wang, X. Q.; Zhang, G. H.; Liu, X. T.; Sun, Z. H.; Sun, G. H.; Wang, L.; Yu, W. T.; Xu, D.



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

PubMed Central

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

Bliss, Timothy V.P.; Cooke, Sam F



Long Term Power System Dynamics. Volume II. Long-Term Power System Dynamics Simulation Program.  

National Technical Information Service (NTIS)

The report describes the Long-Term Dynamic Simulation program (LOTDYS) as it was developed for this project. It is both a programmer's guide and a user's guide for LOTDYS. It contains a list and description of the program variables, the program itself and...



Eosinophilic gastroenteritis in a young girl – long term remission under Montelukast  

Microsoft Academic Search

BACKGROUND: Eosinophilic gastrointestinal disorders are an emerging disease entity characterized by eosinophilic infiltration of the intestinal wall. Oral steroids can be still considered as first line treatment. Unfortunately relapses are quite common. Usually long term low-dose prednisone or immunosuppressive therapy is required, which is especially problematic in young patients. Thus a reliable steroid sparing agent with low side effects suitable

Ivo Quack; Lorenz Sellin; Nikolaus J Buchner; Dirk Theegarten; Lars C Rump; Bernhard F Henning



Long term use of metformin leading to vitamin B 12 deficiency.  


Metformin is a commonly used oral hypoglycaemic agent worldwide. Gastrointestinal side effects and lactic acidosis related to metformin usage are commonly recognized. However, the associated vitamin B12 deficiency is less well known. We present a case of long term metformin use resulting in vitamin B12 deficiency. PMID:24674102

Tung, Moon Ley; Tan, Lip Kun



Where Can You Receive Care? (Long-Term Care)  


... may need. Share page: Where Can You Receive Care? Most long-term care is provided at home. ... in long-term care facilities. Examples of home care services include: An unpaid caregiver who may be ...


Long Term Care Resident Assessment Instrument Training Manual.  

National Technical Information Service (NTIS)

Enclosed are 10 copies of the Long Term Care Resident Assessment Instrument Training Manual for long term care facilities. The manual describes the federally designed resident assessment instrument (RAI) consisting of the minimum data set (MDS) and reside...



Long-Term Maintenance of Weight Loss: Current Status  

Microsoft Academic Search

Intervention strategies for promoting long-term weight loss are examined empirically and conceptually. Weight control research over the last 20 years has dramatically improved short-term treatment efficacy but has been less successful in improving long-term success. Interventions in preadolescent children show greater long-term efficacy than in adults. Extending treatment length and putting more emphasis on energy expenditure have modestly improved long-term

Robert W. Jeffery; Adam Drewnowski; Leonard H. Epstein; Albert J. Stunkard; G. Terence Wilson; Rena R. Wing; Dana Robin Hill




SciTech Connect

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 sensors housed in anti-fouling sensor chambers. The monitoring network is highly versatile and can be applied to a variety of subsurface sensing scenarios in different media. However, the current project focused on monitoring water quality parameters of pH, oxidation-reduction potential, conductivity, and temperature in groundwater.

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



Robotics for Long-Term Monitoring  

SciTech Connect

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-environment surveyor (RHES) is a robotic platform with SCADA capabilities equipped with a sonar-imaging scanner, a high-resolution color CCD camera, and various combinations of sensors. The RHES is controlled remotely via a PC. This paper will discuss the development and application of this system. (authors)

Shahin, Sarkis; Duran, Celso [Florida International University, Miami, Florida (United States)



78 FR 36449 - State Long-Term Care Ombudsman Program  

Federal Register 2010, 2011, 2012, 2013

...1327 RIN 0985-AA08 State Long-Term Care Ombudsman Program AGENCY: Administration...Older Americans Act, the State Long-Term Care Ombudsman program. This proposed rule...compliance in carrying out the Long-Term Care Ombudsman program functions. This...



Long term domiciliary oxygen treatment for chronic respiratory failure reviewed  

Microsoft Academic Search

The use of long term domiciliary oxygen therapy in the Sheffield area from June to August 1987 has been surveyed. Of the 74 patients prescribed long term domiciliary oxygen therapy, 64 were visited at home. These had arterial blood gas tensions or oxygen saturation measured (while breathing oxygen and air), and the indications for long term domiciliary oxygen therapy were

S V Baudouin; J C Waterhouse; T Tahtamouni; J A Smith; J Baxter; P Howard



Physiological evidence for the discrimination of L-arginine from structural analogues by the zebrafish olfactory system.  


Although it is generally assumed that fish are capable of discriminating amino acid odorants on the basis of differences in side-chain structure, less is known about their ability to discriminate amino acids with modifications to alpha-carboxyl and alpha-amino groups. In this study, the ability of the zebrafish olfactory system to detect and presumably discriminate analogues of the basic amino acid Arg was assessed, by using cross-adaptation and activity-dependent labeling techniques. Electrophysiological recordings established that esterification (L-arginine methyl ester; AME) or deletion (agmatine or amino-4-guanidobutane; AGB) of the alpha-carboxyl group yielded odorants more potent than Arg, whereas deletion of the alpha-amino group (L-argininic acid; AA) yielded a less potent analogue. In cross-adaptation experiments, no test-competitor odorant combination yielded complete cross-adaptation, suggesting the detection of these Arg analogues by multiple odorant receptors (ORs) with partially nonoverlapping specificities. Activity-dependent immunocytochemical labeling of olfactory receptor neurons supported this conclusion. AGB, an ion-channel-permeant probe (and odorant), labeled 4.9 +/- 0.4% (n = 24) of sensory epithelium, whereas the addition of Arg, 1-ethylguanidine sulfate, L-alpha-amino-beta-guanidinopropionate, or AME to AGB resulted in a significant elevation of labeling (8-14%). This study provides evidence that the olfactory system has the potential to discriminate among amino acid odorants with modified alpha-carboxyl and alpha-amino groups. PMID:10601449

Lipschitz, D L; Michel, W C



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

NASA Astrophysics Data System (ADS)

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.

Liu, Yun; Yang, Yun; Wu, Feng



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

SciTech Connect

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.

Adams, M.L.; Nock, B.; Truong, R.; Cicero, T.J. (Washington Univ., St. Louis, MO (United States))



Comparative study of the circulatory effects of aminoguanidine and N-nitro-L-arginine in hyperdynamic endotoxemia.  


We have studied the effects of NG-nitro-L-arginine (NNA) a nitric oxide synthase (NOS) inhibitor, and aminoguanidine (AG) a diamine oxidase inhibitor, on hemodynamic parameters and plasma histamine level using a dog model in which a hyperdynamic circulatory response was elicited with a 2-hour infusion of a low dose (13.75 micrograms/kg) of E. coli 055:B5 endotoxin (ETX). AG (50 mg/kg) or NNA (0.5 mg/kg) was administered intravenously as pretreatment. Hemodynamic variables were studied for 4 hours after the beginning of the ETX infusion. The ETX-elicited hyperdynamic response was abolished by NNA and partially inhibited by AG. AG prevented the increases in cardiac output and heart rate and delayed the early decrease in total peripheral resistance (TPR). The plasma histamine concentration elevation was higher in animals receiving AG than in those receiving only ETX. In the group treated with ETX plus NNA the cardiac output was lower and the TPR was higher than in the ETX plus AG group. In future studies, AG should be considered as one of the possible therapeutic tools in sepsis, as its adverse effect on the compensatory hyperdynamic response is less than that of NOS inhibitors of the L-arginine analog type, while it may favourably influence the deleterious excessive activity of the inducible NOS in the later stages. PMID:9046362

Tárnoky, K; Kaszaki, J; Szalay, L; Boros, M; Nagy, S



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


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. PMID:24967545

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




PubMed Central

Experience with the long-term medical management of 17 patients previously subjected to surgical adrenalectomy was reviewed. Maintenance adrenal cortical replacement requirements consisted of oral cortisone, 37.5 to 50 mg. daily in all patients; desoxycorticosterone acetate (DOCA), 2 mg. daily, sublingually in all patients; and supplemental sodium chloride, 1 to 4 grams daily, in seven patients. This provides steroids with glucocorticoid and mineralocorticoid activity and an adequate salt intake. The subjective well-being of the patient was the best indicator of adequate replacement therapy. Under stable conditions, established dosage schedules required surprisingly little adjustment over long periods of time. The primary need of patients without adrenal glands when they are subjected to such stresses as infections, trauma or surgical operation, is for more glucocorticoids. Ordinarily, more DOCA and extra sodium chloride is not required. Mild infections can be dealt with by temporarily increasing the daily oral cortisone requirement, the patient remaining ambulatory. Severe infections with pronounced systemic manifestations require hospitalization and parenteral administration of glucocorticoids. Knowing how long it takes for the various glucocorticoid preparations to take effect and how long they continue to act is important in the management of patients who have had adrenalectomy, particularly in dealing with extraordinary stresses or emergencies.

Simkin, Benjamin



Long-term observations of siamang behaviour.  


Long-term observations are presented on the behaviour of the siamang ape, Symphalangus syndactylus, in the lowland forest of central Malaya. The data were collected during two dry and three fruiting seasons between 1969 and 1973 inclusive on two groups with adjacent ranges; comparisons are made within and between sample periods, and between groups. The influence of weather on daily activities is considered. Food intake is analysed in terms of number of food trees, number of visits to these trees, and the cumulative time spent feeding on various food categories. Ranging behaviour is investigated in terms of distance travelled, area covered, and distribution of time and of food trees about the range. The occurrence of calling is described and compared with that of the white-handed gibbon in the same area. A discussion ensues on each of these aspects of behaviour in turn. Emphasis is laid on the similarity of behaviour of the two groups at any one time, and on the degree of their response to the fluctuations of environment variables. Finally, the application to siamang of ranging concepts currently used in animal behaviour is considered briefly. PMID:1140747

Chivers, D J; Raemaekers, J J; Aldrich-Blake, F P



Bacterial Cellulose: Long-Term Biocompatibility Studies.  


The bacterial cellulose (BC) secreted by Gluconacetobacter xylinus is a network of pure cellulose nanofibres which has high crystallinity, wettability and mechanical strength. These characteristics make BC an excellent material for tissue-engineering constructs, noteworthy for artificial vascular grafts. In this work, the in vivo biocompatibility of BC membranes produced by two G. xylinus strains was analyzed through histological analysis of long-term subcutaneous implants in the mice. The BC implants caused a mild and benign inflammatory reaction that decreased along time and did not elicit a foreign body reaction. A tendency to calcify over time, which may be related to the porosity of the BC implants, was observed, especially among the less porous BC-1 implants. In addition, the potential toxicity of BC nanofibres - obtained by chemical-mechanical treatment of BC membranes - subcutaneously implanted in mice was analysed through bone marrow flow cytometryand histological analyses. At 2 and 4 months post-implantation, the nanofibres implants were found to accumulate intracellularly, in subcutaneous foamy macrophages aggregates. Moreover, no differences were observed between the controls and implanted animals in thymocyte populations and in B lymphocyte precursors and myeloid cells in the bone marrow. PMID:21722421

Pértile, Renata A N; Moreira, Susana; Costa, Rui M Gil da; Correia, Alexandra; Guardão, Luisa; Gartner, Fátima; Vilanova, Manuel; Gama, Miguel



Long-term plutonium storage: Design concepts  

SciTech Connect

An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs.

Wilkey, D.D.; Wood, W.T. [Los Alamos National Lab., NM (United States); Guenther, C.D. [Fluor Daniel, Inc., Irvine, CA (United States)



Long-term corrosion testing pan.  

SciTech Connect

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.

Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)



Long-term corrosion testing plan.  

SciTech Connect

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.

Wall, Frederick Douglas; Brown, Neil R. (Los Alamos National Laboratory, Los Alamos, NM)