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Arginine
Kinds of Arginine Terms modified by Arginine Selected AbstractsArginine-based structures are specific inhibitors of cathepsin CFEBS JOURNAL, Issue 11 2000Application of peptide combinatorial libraries Novel synthetic peptide inhibitors of lysosomal cysteine proteinase cathepsin C have been designed through the use of soluble peptide combinatorial libraries. The uncovered structural inhibitory module consists of the N-terminal cluster of l -arginine residues. Its modification with d -amino acids or arginine derivatives did not increase the inhibition strength. Inhibitory potency of oligoarginines improves with the elongation of peptide chain reaching a maximum for octa- l -arginine. The oligoarginines specifically interact with the cathepsin C active site as shown by competitive-type inhibition kinetics (Ki , 10,5 m) and intrinsic fluorescence measurements. The inhibitory interaction of oligoarginines is established through the specific spatial contact of a net of guanidino groups in the arginine side-chains, as indicated by comparison with inhibitory action of low molecular mass guanidine derivatives (Ki , 10,3 m). Nonarginine polyionic compounds cannot mimic the inhibitory effect of oligoarginines. The arginine-based peptide inhibitors were selective towards cathepsin C among other cysteine proteinases tested. [source] Tyrosine phosphorylation of a 38-kDa capacitation-associated buffalo (Bubalus bubalis) sperm protein is induced by L -arginine and regulated through a cAMP/PKA-independent pathwayINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2008S. C. Roy Summary The aim of the present study was to determine the effect of l -arginine on nitric oxide (NO,) synthesis, capacitation and protein tyrosine phosphorylation in buffalo spermatozoa. Ejaculated buffalo spermatozoa were capacitated in the absence or presence of heparin, or l -arginine or N, -nitro- l -arginine methyl ester (l -NAME), an inhibitor of nitric oxide synthase (NOS) for 6 h. Capacitating spermatozoa generated NO, both spontaneously and following stimulation with l -arginine and l -NAME quenched such l -arginine-induced NO, production. Immunolocalization of NOS suggested for existence of constitutive NOS in buffalo spermatozoa. l -Arginine (10 mm) was found to be a potent capacitating agent and addition of l -NAME to the incubation media attenuated both l -arginine and heparin-induced capacitation and suggested that NO, is involved in the capacitation of buffalo spermatozoa. Two sperm proteins of Mr 38 000 (p38) and 20 000 (p20) were tyrosine phosphorylated extensively by both heparin and l -arginine. Of these, the tyrosine phosphorylation of p38 was insensitive to both induction by cAMP agonists as well as inhibition by a protein kinase A (PKA) inhibitor. Further, most of these l -arginine-induced tyrosine phosphorylated proteins were localized to the midpiece and principal piece regions of flagellum of capacitated spermatozoa and suggested that sperm flagellum takes active part during capacitation. These results indicated that l -arginine induces capacitation of buffalo spermatozoa through NO, synthesis and tyrosine phosphorylation of specific sperm proteins involving a pathway independent of cAMP/PKA. [source] Sensory aroma from Maillard reaction of individual and combinations of amino acids with glucose in acidic conditionsINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 9 2008Kam Huey Wong Summary The aroma produced in glucose,amino acids (individual and in combination) Maillard reaction, under acidic conditions at 100 °C were determined and compared by trained panellist. Proline produced pleasant, flowery and fragrant aroma. Phenylalanine and tyrosine produced dried roses aroma. Alanine produced fruity and flowery odour, while aspartic acid and serine both produced pleasant, fruity aroma. Arginine, produced a pleasant, fruity and sour aroma at pH 5.2, but not at its natural pH. Glycine, lysine, threonine and valine produced a pleasant caramel-like odour. Isoleucine and leucine gave off a burnt caramel aroma. Methionine developed a fried potato odour. Cysteine and methionine produced savoury, meaty and soy sauce-like flavours. A combination of these amino acids produced different types of aroma, with the stronger note dominating the odour of the mixture. This study will help the prediction of flavour characteristics of hydrolysates from different protein sources. [source] Identification of Candidate Amino Acids Involved in the Formation of Blue Pigments in Crushed Garlic Cloves (Allium sativum L.)JOURNAL OF FOOD SCIENCE, Issue 1 2009Jungeun Cho ABSTRACT:, The color-forming ability of amino acids with thiosulfinate in crushed garlic was investigated. We developed reaction systems for generating pure blue pigments using extracted thiosulfinate from crushed garlic and onion and all 22 amino acids. Each amino acid was reacted with thiosulfinate solution and was then incubated at 60 °C for 3 h to generate pigments. Unknown blue pigments, responsible for discoloration in crushed garlic cloves (Allium sativum L.), were separated and tentatively characterized using high-performance liquid chromatography (HPLC) and a diode array detector ranging between 200 and 700 nm. Blue pigment solutions exhibited 2 maximal absorbance peaks at 440 nm and 580 nm, corresponding to yellow and blue, respectively, with different retention times. Our findings indicated that green discoloration is created by the combination of yellow and blue pigments. Eight naturally occurring blue pigments were separated from discolored garlic extracts using HPLC at 580 nm. This suggests that garlic discoloration is not caused by only 1 blue pigment, as reported earlier, but by as many as 8 pigments. Overall, free amino acids that formed blue pigment when reacted with thiosulfinate were glycine, arginine, lysine, serine, alanine, aspartic acid, asparagine, glutamic acid, and tyrosine. Arginine, asparagine, and glutamine had spectra that were more similar to naturally greened garlic extract. [source] Arginine facilitates inactivation of enveloped virusesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2008Hisashi Yamasaki Abstract Virus inactivation is a key step for the purification of pharmaceutical proteins derived from recombinant mammalian expression systems and conventionally done using low pH-treatment, which is often harmful to the proteins to be purified. This is particularly true for antibodies, because immunoglobulin proteins undergo conformational changes at acidic pH. We have been developing mild elution solvents using arginine for Protein-A chromatography to minimize the low pH-induced damages on the antibodies. Here we have tested the aqueous solutions containing arginine or butyroyl-arginine at or above pH 4.0 for their effects on virus inactivation, since these solvents are effective above pH 4.0 in elution of bound antibodies from Protein-A columns. When the virus was incubated on ice, 0.1 M sodium citrate was totally ineffective above pH 4.0, but aqueous solutions containing arginine above 0.35 M or butyroyl-arginine above 0.28 M showed extensive virus killing at or even above pH 4.0. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 3067,3073, 2008 [source] Plasma Asymmetric Dimethylarginine, Symmetric Dimethylarginine, l -Arginine, and Nitrite/Nitrate Concentrations in Cats with Chronic Kidney Disease and HypertensionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2008R.E. Jepson Background: Chronic kidney disease (CKD) and hypertension have been associated with decreased bioavailability of nitric oxide (NO) and endothelial dysfunction. Increased concentrations of the endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) are implicated. Hypothesis: Plasma ADMA concentration is increased in cats with CKD and systemic hypertension corresponding to a decrease in total plasma nitrate/nitrite (NOx) availability. Decrease in systolic blood pressure (SBP) and proteinuria during treatment of hypertension with amlodipine besylate may be associated with increased NOx availability. Animals: Sixty-nine client-owned normotensive and hypertensive cats with variable azotemia. Methods: Plasma ADMA, symmetric dimethylarginine (SDMA), and l -arginine were measured simultaneously by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry in cats from 6 groups: normotensive nonazotemic (n = 10), normotensive mildly azotemic (n = 10), hypertensive mildly azotemic with hypertensive retinopathy (n = 20), hypertensive mildly azotemic without hypertensive retinopathy (n = 10), normotensive moderately azotemic cats (n = 10), and hypertensive nonazotemic cats (n = 9). Plasma NOx concentrations were measured. Results: A moderate correlation between plasma creatinine and ADMA (n = 69, r= .608, P < .001), SDMA (n = 69, r= .741, P < .001), and NOx concentrations (n = 69, r= .589, P < .001) was observed. There was no association among plasma ADMA, SDMA, and NOx concentrations and SBP. Conclusions and Clinical Importance: Plasma ADMA and SDMA concentrations are increased in cats with CKD and correlate with plasma creatinine concentration. This may imply the presence of endothelial dysfunction in cats with CKD. Plasma ADMA concentrations were not associated with systemic hypertension. Treatment of systemic hypertension with amlodipine besylate did not affect plasma ADMA or NOx concentrations. [source] Extracellular Arginine Rapidly Dilates In Vivo Intestinal Arteries and Arterioles Through a Nitric Oxide MechanismMICROCIRCULATION, Issue 2 2008Laura Pezzuto ABSTRACT Objective: Arginine used for nitric oxide formation can be from intracellular stores or transported into cells. The study evaluated the rapidity, and primary site of NO and vascular resistance responses to arginine at near physiological concentrations (100,400 , M). Methods: Arginine was applied to a single arteriole through a micropipette to determine the fastest possible responses. For vascular blood flow and [NO] responses, arginine was added to the bathing media. Results: Dilation of single arterioles to arginine began in 10,15 seconds and application over the entire vasculature increased [NO] in , 60,90 seconds, and flow increased within 120,300 seconds. Resting periarteriolar [NO] for arterioles was 493.6 ± 30.5 nM and increased to 696.1 ± 68.2 and 820.1 ± 110.5 nM at 200 and 400 , M L-arginine. The blood flow increased 50% at 400,1200 , M L-arginine. The reduced arterial resistance during topical arginine was significantly greater than microvascular resistance at 100 and 200 , M arginine. All responses were blocked by L-NAME. Conclusions: This study demonstrated arterial resistance responses are as or more responsive to arginine induced NO formation as arterioles at near physiological concentrations of arginine. The vascular NO and resistance responses occurred rapidly at L-arginine concentrations at and below 400 , M, which predict arginine transport processes were involved. [source] The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesisMOLECULAR CARCINOGENESIS, Issue 2 2006Hagit F. Yerushalmi Abstract Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc -dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of ApcMin/+Nos2+/+ mice. NOS3 expression was higher in intestinal tissues of mice lacking Nos2, mainly in the small intestine. When diet was supplemented with arginine (0.2% and 2% in drinking water), lack of Nos2 results in decreased tumorigenesis in both small intestine and colon. In Nos2 knockout mice, supplemental arginine (up to 2%) caused a decrease in small intestinal tumor number and size. The arginine-dependent decrease was associated with an increase in nitrotyrosine formation and apoptosis in the region of intestinal stem cells. Mice expressing Nos2 did not show these changes. These mice did, however, show an arginine-dependent increase in colon tumor number and incidence, while no effect on apoptosis was seen. These changes were associated with increased nitrotyrosine formation in epithelial cells. Mice lacking Nos2 did not show changes in tumorigenesis or nitrotyrosine formation, while demonstrating an arginine-dependent increase in apoptosis. These data suggest that Nos2 and dietary arginine have significant effects on intestinal and colonic tumorigenesis in Min mice. In both tissues, loss of Nos2 is associated with decreased tumorigenesis when mice are supplemented with dietary arginine. In the small intestine, Nos2 prevents the arginine-induced decrease in tumor number and size, which is associated with NOS3 expression and increased apoptosis. In the colon, Nos2 is required for the arginine-induced increase in tumor number and incidence. © 2005 Wiley-Liss, Inc. [source] Latest news and product developmentsPRESCRIBER, Issue 10 2008Article first published online: 3 JUN 200 Glitazones more than double fracture risk An analysis of the UK General Practice Research Database has found that both glitazones increase the risk of fracture more than two-fold (Arch Intern Med 2008;168:820-5). Compared with nonusers, the odds ratio for fracture (mostly hip and wrist) was 2.59 for pioglitazone and 2.38 for rosiglitazone. The risk increased with dose but was unrelated to age and sex. Reduce antipsychotics in dementia patients Antipsychotics should be prescribed for patients with dementia only as a last resort at times of severe distress or critical need, the All-Party Parliamentary Group on Dementia has concluded. Its inquiry (available at www.alzheimers.org.uk) found that antipsychotics are being prescribed for patients with mild behavioural symptoms and for prolonged periods despite the limited benefits they offer and the risk of serious adverse effects such as stroke. Contributory factors include lack of training for staff, inadequate leadership and exclusion of family and friends from decisions about treatment. High-dose atorvastatin in chronic kidney disease High-dose atorvastatin (Lipitor) reduces cardiovascular events in patients with chronic kidney disease (CKD) more than a low dose , despite similar reductions in LDL-C (J Am Coll Cardiol 2008;51:1448-54). A post hoc subgroup analysis of the Treating-to-New-Targets study involving 10 001 patients with CHD, with or without CKD, found that atorvastatin 10 and 80mg per day reduced LDLC and triglycerides to similar levels; there was no change in HDL-C. After a median follow-up of five years, the incidence of cardiovascular events in patients with CKD was 9.3 per cent at 80mg per day and 13.4 per cent at 10mg per day (number needed to treat to prevent one event, NNT, 24). In patients with no CKD, the corresponding figures were 7.9 vs 9.2 per cent (NNT 74). There was no difference in all-cause mortality; adverse events were more frequent at the higher dose. COX-2 NSAIDs not more cost-effective An economic analysis of COX-2 selective NSAIDs has concluded that they are not more cost effective than older agents plus a proton pump inhibitor (PPI) in the treatment of osteoarthritis and rheumatoid arthritis (Health Technology Assessment 2008;12:No. 11). The analysis concluded that selective and nonselective NSAIDs were similarly effective but selective agents were associated with a lower risk of upper GI events and a higher risk of cardiovascular events. However, the available evidence includes only low numbers of events and further studies are needed. Compared with ibuprofen or diclofenac plus a PPI, the COX-2 selective NSAIDs look ,generally unattractive from a cost effectiveness point of view', even in high-risk patients with a history of peptic ulcer. There were insufficient data to allow a reliable comparison within the COX-2s. Naftidrofuryl helps intermittent claudication Naftidrofuryl increases pain-free walking distance (PFWD) in patients with intermittent claudication, a new Cochrane review has shown (Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD001368. DOI: 10.1002/ 14651858.CD001368.pub3; also see page 49 in this issue). The meta-analysis of six trials involving a total of 1083 patients found that, compared with placebo, naftidrofuryl increased PFWD by over a third with a proportion successfully treated of 20 per cent (NNT 4.5). Coversyl Arginine To clarify any confusion following our recent news item (Perindopril brand switch, 19 April issue, page 12), Servier has asked us to reiterate that the new formulations Coversyl Arginine 2.5, 5 and 10mg are equivalent to 2, 4 and 8mg of the discontinued Coversyl formulation. Coversyl Arginine contains perindopril arginine, a salt that offers greater stability and a longer shelf-life. Prescriptions for the Coversyl brand of perindopril must in future be written as Coversyl Arginine in its revised strengths. Coversyl Plus has also been replaced by Coversyl Arginine Plus and the same revised dosages apply. Generic formulations of perindopril remain unaffected. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Arginine test is not reliable for diagnosing cerebellar multiple system atrophyANNALS OF NEUROLOGY, Issue 3 2010Raquel C. Gardner MD We evaluated the arginine growth hormone (GH) stimulation test for the diagnosis of cerebellar-type multiple system atrophy (MSAc) in patients with ataxia. Fourteen subjects with MSAc, 11 with idiopathic late-onset cerebellar ataxia (ILOCA), 10 with familial ataxia, and 10 healthy controls were tested. After pituitary GH deficiency was excluded, subjects underwent arginine testing. Peak serum GH response was analyzed. No significant differences in peak GH response were found between subject populations. Thirty-three percent of MSAc subjects mounted responses >10,g/l GH. Thirty-six percent of ILOCA subjects and 40 percent of healthy controls mounted responses <4,g/l GH. Arginine thus appears to be unreliable for the diagnosis of MSAc. ANN NEUROL 2010;67:404,408 [source] Determination of microbial community structures of shrimp floc cultures by biomarkers and analysis of floc amino acid profilesAQUACULTURE RESEARCH, Issue 2 2008Zhi Yong Ju Abstract Simple, rapid and reliable methods are required to monitor the microbial community change in aquatic pond for better animal performance. Four floc (suspended organic matter) samples were collected from outdoor raceways and tanks used for culturing Pacific white shrimp Litopenaeus vannamei. Twenty-two chlorophyll (Chl) and carotenoid pigments were separated, identified and quantified using high-performance liquid chromatography,ultraviolet/Vis-mass spectrometry in the freeze-dried floc samples. Algal community composition (diatoms, chlorophytes, cyanobacteria, dinoflagellates and cryptophytes) was determined by measuring concentrations of the respective taxonomic biomarkers (carotenoid fucoxanthin, lutein, zeaxanthin, peridinin and alloxanthin) as independent variables and Chl a as the dependent variable using a multiple regression model. This analysis found that the phytoplankton community of the floc samples from two groups of shrimp tanks (32 g L,1 -salinity) were diatom-dominated (81.7% and 84.4%); and two floc samples from shrimp raceways (5 and 18 g L,1 -salinity) were chlorophyte-dominated (75.4% and 82.3%). Assessment of total algal and bacterial biomass by quantification of Chl a and muramic acid, respectively, indicated that the 18 g L,1 -salinity raceway sample was bacteria-dominated, whereas the other three floc samples were algae-dominated. Sample protein quality was evaluated by its essential amino acid (AA) score and index. Arginine and lysine were found to be the two most limiting AAs for all floc samples. [source] Control of non-adrenergic non-cholinergic reflex motor responses in circular muscle of guinea-pig small intestine by Met-enkephalinAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2002Chr. Ivancheva Summary 1 A triple organ bath method allowing the synchronous recording of the motor activity of the circular muscle layer belonging to the oral and anal segments of guinea-pig small intestine adjacent to an electrically stimulated middle segment was developed to study the ascending and descending reflex motor responses. 2 Electrical field stimulation (0.8 ms, 40 V, 5 Hz, 10 s) applied to the middle part of the segments elicited tetrodotoxin (1 ,m)-sensitive ascending and descending contractile responses of the nonstimulated parts, oral and anal, respectively. The ascending contraction was more pronounced as compared with the descending contraction. 3 In the presence of phentolamine (5 ,m), propranolol (5 ,m) and atropine (3 ,m) a significant decrease in the amplitude of the ascending contraction was seen and a descending relaxation, instead of a contraction was observed. 4 Met-enkephalin applied at a single concentration (0.1 ,m) or cumulatively (0.001,1 ,m) inhibited both non-adrenergic non-cholinergic (NANC) descending relaxation and ascending contraction with similar efficacy but different potency, IC50 being 5.9 ± 0.3 and 39.0 ± 4 nm, respectively. Naloxone (0.5 ,m) prevented the effects of Met-enkephalin. 5 L-NNA (0.5 mm), an inhibitor of nitric oxide synthesis, increased the ascending contraction and strongly reduced but not abolished the descending relaxation. l -Arginine (0.5 mm) restored the motor responses to the initial level in l -NNA-pretreated preparations, d -Arginine (0.5 nm) had no effects. 6 Met-enkephalin (0.1 ,m) depressed the l -NNA-dependent increase of the ascending contraction and failed to change the l -NNA-resistant part of the descending relaxation. 7 Met-enkephalin did not alter spontaneous NANC mechanical activity. SNP (1 or 10 ,m), an exogenous donor of nitric oxide, caused a concentration-dependent relaxation. The effects of SNP persisted in Met-enkephalin (0.1 ,m)-pretreated preparations. 8 NANC reflex ascending contraction and descending relaxation were synchronously induced by a local nerve stimulation indicating a functional coactivation of NANC orally projected excitatory and anally directed inhibitory pathways. Acting prejunctionally, Met-enkephalin provided a negative controlling mechanism inhibiting both ascending and descending, mainly nitric oxide mediated, reflex responses. A higher sensitivity of the descending relaxation to Met-enkephalin was observed suggesting an essential role of opioid(s) in reducing the efficacy of descending motor activity. [source] Role of Arginine in Protein Refolding, Solubilization, and PurificationBIOTECHNOLOGY PROGRESS, Issue 5 2004Kouhei Tsumoto Recombinant proteins are often expressed in the form of insoluble inclusion bodies in bacteria. To facilitate refolding of recombinant proteins obtained from inclusion bodies, 0.1 to 1 M arginine is customarily included in solvents used for refolding the proteins by dialysis or dilution. In addition, arginine at higher concentrations, e.g., 0.5,2 M, can be used to extract active, folded proteins from insoluble pellets obtained after lysing Escherichia coli cells. Moreover, arginine increases the yield of proteins secreted to the periplasm, enhances elution of antibodies from Protein-A columns, and stabilizes proteins during storage. All these arginine effects are apparently due to suppression of protein aggregation. Little is known, however, about the mechanism. Various effects of solvent additives on proteins have been attributed to their preferential interaction with the protein, effects on surface tension, or effects on amino acid solubility. The suppression of protein aggregation by arginine cannot be readily explained by either surface tension effects or preferential interactions. In this review we show that interactions between the guanidinium group of arginine and tryptophan side chains may be responsible for suppression of protein aggregation by arginine. [source] Effects of oral L -arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2008Zekiye Sultan Altun Abstract 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. Copyright © 2008 John Wiley & Sons, Ltd. [source] The Role of Arginine 28 in Catalysis by Dihydrofolate Reductase from the Hyperthermophile Thermotoga maritimaCHEMBIOCHEM, Issue 16 2009E. Joel Loveridge Dr. Get a grip: Dihydrofolate reductase from Thermotoga maritima (TmDHFR) is unusual in that it has an arginine residue within its active site (ringed residue). Here, we address the role of this residue in catalysis. We find no evidence that Arg28 compromises catalysis in TmDHFR by preventing protonation of the substrate or that it acts as an acid to protonate the substrate. Instead, it appears that this residue plays an important role in binding the substrate tightly to ensure its thermal stability. [source] ChemInform Abstract: Protonated Arginine and Lysine as Catalysts for the Direct Asymmetric Aldol Reaction in Ionic Liquids.CHEMINFORM, Issue 10 2009Marco Lombardo Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Relationship of peak growth hormone to cardiovascular parameters, waist circumference, lipids and glucose in HIV-infected patients and healthy adultsCLINICAL ENDOCRINOLOGY, Issue 6 2009Janet Lo Summary Objective, Relative growth hormone (GH) deficiency is highly prevalent in patients with HIV. The purpose of this study was to investigate relationships of GH to metabolic and anthropometric parameters in HIV patients and non-HIV controls. Design, Peak GH and metabolic parameters were assessed in a cross-sectional study of 191 HIV patients and 62 age and BMI-matched healthy controls. Methods, Peak GH was assessed by GHRH/arginine stimulation testing. Results, HIV patients demonstrated similar BMI, but increased waist circumference (WC) and reduced peak GH to GHRH/arginine compared with control subjects [median = 12·4 (interquartile range: 6·3,24·8) vs. 21·3 (8·8, 34·5) ,g/l, P = 0·006, HIV vs. control]. Among HIV and non-HIV groups, peak GH was inversely associated with WC (rho = ,0·44, P < 0·0001; rho = ,0·63, P < 0·0001; HIV patients and controls, respectively), blood pressure (rho = ,0·17, P = 0·02; rho = ,0·36, P = 0·004), triglycerides (rho = ,0·37, P < 0·0001; rho = ,0·43, P = 0·001), glucose (rho = ,0·34, P < 0·0001; rho = ,0·30, P = 0·02), insulin (rho = ,0·43, P < 0·0001; rho = ,0·60, P < 0·0001) and CRP (rho = ,0·29, P < 0·0001; rho = ,0·59, P < 0·0001). Among HIV patients, the inverse association between peak GH and fasting glucose remained significant (, = ,0·006 mmol/l change in glucose per ,g/l change in GH, P = 0·004) controlling for age, gender, race, BMI, WC, protease inhibitor (PI) and nucleoside reverse transcriptase inhibitors. Similarly, the inverse association between peak GH and triglycerides remained significant (, = ,0·01 mmol/l change in triglycerides per ,g/l change in GH, P = 0·02) controlling for age, gender, race, BMI, WC, PI and lipid-lowering medications. HIV men with peak GH < 7·5 ,g/l demonstrated higher BMI, WC, SBP, triglycerides, glucose and CRP. Conclusions, Reduced GH secretion is independently associated with dyslipidaemia and higher glucose, among HIV patients with abdominal fat accumulation. [source] Nitric oxide, superoxide and renal blood flow autoregulation in SHR after perinatal L -arginine and antioxidantsACTA PHYSIOLOGICA, Issue 4 2007M. P. Koeners Abstract Aim:, Nitric oxide (NO) and superoxide are considered to be regulatory in renal blood flow (RBF) autoregulation, and hence may contribute to development of hypertension. To extend our previous observations that dynamic NO release is impaired in the spontaneously hypertensive rat (SHR) we investigated, firstly, if superoxide dependency of RBF autoregulation is increased in SHR and, secondly, if the beneficial effect of perinatal supplementation in SHR is partly as a result of early correction of RBF autoregulation. We hypothesized that perinatal supplementation by restoring dynamic NO release and/or decreasing superoxide dependency and would improve life-long blood pressure regulation. Methods:, Autoregulation was studied using stepwise reductions in renal perfusion pressure in anaesthetized male SHR, SHR perinatally supplemented with arginine and antioxidants (SHRsuppl) and Wistar-Kyoto (WKY), prior to and during i.v. N, -nitro- l -arginine (NO synthase inhibitor) or tempol (superoxide dismutase mimetic). Results:, Spontaneously hypertensive rat displayed a wider operating range of RBF autoregulation as compared with WKY (59 ± 4 vs. 33 ± 2 mmHg, respectively; P < 0.01). Perinatal supplementation in SHR decreased mean arterial pressure, renal vascular resistance and the operating range of RBF autoregulation (43 ± 3 mmHg; P < 0.01). In addition autoregulation efficiency decreased. RBF autoregulation characteristics shifted towards those of normotensive WKY. However, dynamic NO release was still impaired and no clear differences in superoxide dependency in RBF autoregulation between groups was observed. Conclusion:, Perinatal supplements shifted RBF autoregulation characteristics of SHR towards WKY, although capacity of the SHRsuppl kidney to modulate NO production to shear stress still seems impaired. The less strictly controlled RBF as observed in perinatally supplemented SHR could result in an improved long-term blood pressure control. This might partly underlie the beneficial effects of perinatal supplementation. [source] Changes in reactivity of rat arteries subjected to dynamic stretchACTA PHYSIOLOGICA, Issue 1 2000Dvoretsky The effect of dynamic stretch on the reactivity of the rat tail and mesenteric artery segments was studied. Segments mounted on a myograph were stretched by a computer-controlled motorized micromanipulator. Dynamic stretch (1, 5 or 7 Hz) inhibited the artery constriction induced by noradrenaline (10 ,M), 5-hydroxytryptamine (0.7 ,M), or electrical field stimulation of intramural nerves. In contrast, dynamic stretch enhanced the tetrodotoxin-insensitive dilation induced by electrical field stimulation of noradrenaline-contracted arteries. Maximal increase of dilation evoked by electrical field stimulation (24.5 ± 5.0% in mesenteric and 50.3 ± 15.6% in the tail artery) was observed at a dynamic stretch-frequency of 5 Hz. An inhibitor of nitric oxide synthesis, NG -nitro- L -arginine (100 ,M), abolished the difference in reactivity between static and dynamic conditions. The results indicate that dynamic stretch of the arteries activates nitric oxide synthesis/secretion, thus reducing constrictor and increasing dilator responses to the stimuli used. [source] Advanced glycation endproducts: what is their relevance to diabetic complications?DIABETES OBESITY & METABOLISM, Issue 3 2007N. Ahmed Glycation is a major cause of spontaneous damage to proteins in physiological systems. This is exacerbated in diabetes as a consequence of the increase in glucose and other saccharides derivatives in plasma and at the sites of vascular complications. Protein damage by the formation of early glycation adducts is limited to lysine side chain and N-terminal amino groups whereas later stage adducts, advanced glycation endproducts (AGEs), modify these and also arginine and cysteine residues. Metabolic dysfunction in vascular cells leads to the increased formation of methylglyoxal which adds disproportionately to the glycation damage in hyperglycaemia. AGE-modified proteins undergo cellular proteolysis leading to the formation and urinary excretion of glycation free adducts. AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE-modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein,protein and enzyme,substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents. Increasing expression of enzymes of the enzymatic defence against glycation provides a novel and potentially effective future therapeutic strategy to suppress protein glycation. [source] Lack of CbrB in Pseudomonas putida affects not only amino acids metabolism but also different stress responses and biofilm developmentENVIRONMENTAL MICROBIOLOGY, Issue 6 2010Cristina I. Amador Summary The CbrAB two-component system has been described in certain species of Pseudomonads as a global regulatory system required for the assimilation of several amino acids (e.g. histidine, proline or arginine) as carbon or carbon and nitrogen sources. In this work, we used global gene expression and phenotypic analyses to characterize the roles of the CbrAB system in Pseudomonas putida. Our results show that CbrB is involved in coordination with the nitrogen control system activator, NtrC, in the uptake and assimilation of several amino acids. In addition, CbrB affects other carbon utilization pathways and a number of apparently unrelated functions, such as chemotaxis, stress tolerance and biofilm development. Based on these new findings, we propose that CbrB is a high-ranked element in the regulatory hierarchy of P. putida that directly or indirectly controls a variety of metabolic and behavioural traits required for adaptation to changing environmental conditions. [source] A metagenomic analysis of soil bacteria extends the diversity of quorum-quenching lactonasesENVIRONMENTAL MICROBIOLOGY, Issue 3 2008Kashif Riaz Summary A metagenomic library of 10 121 clones, generated from bacteria inhabiting a pasture soil from France, was screened for the presence of fosmids conferring either N -acylhomoserine lactone (NAHL) synthesis or NAHL degradation ability upon their Escherichia coli host. No clone producing NAHLs was identified whereas one, containing a 31 972 bp insert in fosmid p2H8, allowed NAHL degradation. This led to the cloning and identification of a gene, qlcA, encoding an NAHL-lactonase activity, as judged by lactone-ring closure and HPLC/MS analyses of NAHL degradation products. The qlcA gene efficiently quenched quorum-sensing regulated pathogenic functions when expressed in Pectobacterium carotovorum. The QlcA peptide belongs to the family of zinc-dependent metallohydrolases and appears to be distantly related to other NAHL-lactonases discovered in Agrobacterium, Bacillus, Photorhabdus and Rhizobium. In-silico analysis of the metagenomic insert revealed the occurrence of 20 orf, with a constant GC% and codon usage, suggesting a unique bacterial origin. Nine out of these 20 orf were homologous to genes encoding biosynthesis of arginine; they were clustered with an unusual succession argFJADBCRGH. The fosmid p2H8 is able to complement the argA, argB and argC mutants in E. coli. Phylogenetic analysis showed that 9 orf out of 20 were related to sequences from members of the Acidobacteria, supporting the hypothesis that the analysed insert might be originated from an organism related to this phylum. [source] A green light-absorbing phycoerythrin is present in the high-light-adapted marine cyanobacterium Prochlorococcus sp.ENVIRONMENTAL MICROBIOLOGY, Issue 10 2005Summary In the high-light-adapted unicellular marine cyanobacterium Prochlorococcus sp. MED4 the cpeB gene is the only gene coding for a structural phycobiliprotein. The absence of any other phycoerythrin gene in the fully sequenced genome of this organism, the previous inability to detect a gene product, and the mutation of two out of four cysteine residues, normally involved in binding chromophores, suggested that MED4- cpeB might not code for a functional protein. Here, transcription of MED4- cpeB at a low level was detected and the transcriptional start site was mapped. Enrichment of the protein identified phycoerythrobilin as its sole chromophore in vivo, which was confirmed by chromophorylation assays in vitro using the recombinant protein. Phycourobilin is the major chromophore in low-light-adapted Prochlorococcus ecotypes such as strain SS120. Therefore, spectrally tuned phycoerythrins are a characteristic feature of distinct Prochlorococcus ecotypes. Further in vitro mutagenesis experiments replacing one or both cysteines C61R/C82S by arginine or serine, respectively, revealed that only Cys82 is required for chromophore binding. Thus, an unusual green light-absorbing phycoerythrin evolved in the high-light-adapted ecotypes of Prochlorococcus, which potentially serves as a photoreceptor. [source] Microcystin-LR modulates selected immune parameters and induces necrosis/apoptosis of carp leucocytes,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010Anna Rymuszka Abstract Microcystins (MCs) are potent hepatotoxins acting by the inhibition of protein phosphatase 1 and 2A, and may promote liver tumors. Moreover, studies also suggest they are nephrotoxic. The aim of the present study was to assess possible in vitro effects of microcystin-LR (which contains the amino acids leucine and arginine, the most widely studied and distributed variant of all microcystins) on the selected immune functions of the cells isolated from the head kidney of carp. In the experiments, pure microcystin-LR (MC-LR), was used at concentrations of 0.01, 0.1, 0.5, and 1,µg/ml RPMI-1640 medium. Leucocytes (lymphocytes and phagocytes) were isolated by centrifugation on a density gradient. Lymphocyte proliferation, intracellular production of reactive oxygen species by phagocytes, and the presence of apoptotic and/or necrotic cells were assessed. The respiratory burst activity of phagocytic cells was increased at the lowest toxin concentration used in the study, but it was decreased at higher concentrations. Using a sensitive luminescent immunoassay, MC-LR was observed to have no influence on the T-cell proliferation but decreased the proliferation of B lymphocytes. Moreover, it was noted that MC-LR induced necrosis to a higher degree than apoptosis in fish leucocytes. The results of the present study suggest the modulatory potency of microcystin-LR on fish leucocytes. Environ. Toxicol. Chem. 2010;29:569,574. © 2009 SETAC [source] Effects of dietary N -acetylcysteine on the oxidative stress induced in tilapia (Oreochromis Niloticus) exposed to a microcystin-producing cyanobacterial water bloom,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2009María Puerto Abstract Fish can be exposed to toxic cyanobacterial cells in natural waters and fish farms and suffer from oxidative damage. The present study investigates the effects of N-acetylcysteine (NAC), a glutathione (GSH) precursor, on the oxidative stress induced by Microcystis cyanobacterial cells containing microcystins (MCs) in tilapia fish (Oreochromis niloticus). Variation in lipid peroxidation (LPO) levels, carbonyl group content, reduced glutathione to oxidized glutathione ratio (GSH: GSSG), and catalase (Enzyme Commission [EC] 1.11.1.6), superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.8.1.7), glutathione peroxidase (GPx; EC 1.11.1.9), and glutathione S-transferase (EC 2.5.1.18) activities in liver and kidney of tilapia exposed to a single oral dose of 120 ,g MC-LR (with leucine [L] and arginine [R])/fish and killed in 24 h were investigated in the absence and presence of 20.0, 44.0, and 96.8 mg NAC/fish/d. Results showed a protective role of NAC, depending on the dose and the biomarker considered. The increase in LPO (1.9-and 1.4-fold in liver and kidney, respectively) and the decreased protein content and GSH:GSSG in the liver induced by MCs were recovered mainly by the lower doses of NAC employed. Antioxidant enzyme activities increased (range, 1.4-to 1.7-fold) by MCs also were ameliorated by NAC, although the highest level used induced significant alteration of some enzymatic activities, such as SOD, GPx, and GR. Thus, NAC can be considered to be a useful chemoprotectant that reduces hepatic and renal oxidative stress in the prophylaxis and treatment of MC-related intoxications in fish when careful attention is given to its application dose because of its own pro-oxidant activity, as shown in the present study at 96.8 mg NAC/ fish/d. [source] Role of Nitric Oxide in Pentylenetetrazol-Induced Seizures: Age-Dependent Effects in the Immature RatEPILEPSIA, Issue 4 2000Anne Pereira de Vasconcelos Summary: Purpose: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)-induced seizures in immature rats. Methods: Four cortical electrodes were implanted in 10-day-old (P10) and 21-day-old (P21) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of NG -nitro- l -arginine methyl ester (l -NAME; 10 mg/kg) and 7-nitroindazole (7NI; 40 mg/kg), two NO synthase (NOS) inhibitors, and l -arginine (l -arg; 300 mg/kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate. Results: At P10, the postseizure mortality rate increased from 18,29% for the rats receiving PTZ only to 100% and 89% for the rats receiving l -NAME and 7NI, respectively; whereas l -arg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82,89% mortality rate induced by PTZ alone, whereas l -arg decreased the mortality rate to 29%. In addition, all NO-related drugs increased the duration of ictal activity at P10, whereas at P21, L -arg and L -NAME affected the first seizure type, producing clonic seizures with L -arg and tonic seizures with L -NAME. Conclusions: The relative natural protection of very immature rats (P10) against PTZ-induced deaths could be linked to a high availability of L -arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO-related compounds may be related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of clonic seizures. [source] Fatty acid incorporation in endothelial cells and effects on endothelial nitric oxide synthaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2007S. Couloubaly Abstract Background The nature of fatty acids provided by the diet as well as plasma lipid metabolism can modify the composition and properties of plasma membrane and thus the activity of membrane proteins. In humans, as well as in experimental models, diabetes is associated with both an alteration in serum lipid profile and a documented endothelial dysfunction. This in vitro study investigated on an immortalized human endothelial cell line (EA.hy 926) the specific effects of several free fatty acids (FFAs) on the composition of cellular membranes and the regulation of endothelial nitric oxide synthase (eNOS). Materials and methods 0·1% of lipid deprived serum was added to the incubation medium with 25 mm glucose in order to study the effects of individual fatty acids: myristic acid, palmitic acid, stearic acid, oleic acid or linoleic acid at 100 µm bound with albumin. The effects of the FFAs on the endothelial nitric oxide synthase were investigated on mRNA level by quantitative PCR, on protein level and Ser1177 phosphorylation by Western blot and on enzymatic activity on living cells using radiolabelled arginine. Results Free linoleic acid increased the membrane content in n-6 fatty acids (mainly C18: n-6 and its metabolites) with a decrease in saturated and monounsaturated fatty acids. These conditions decreased the basal eNOS activity and reduced the phosphorylation of eNOS-Ser1177 due to activation by histamine. Free palmitic acid enriched the membranes with 16 : 0 with a slight decrease in monounsaturated fatty acids. These conditions increased eNOS activation without increasing Ser1177 phosphorylation upon histamine activation. The addition of the other FFAs also resulted in modifications of membrane composition, which did not to affect eNOS-Ser1177 phosphorylation. Conclusion Among the fatty acids used, only modification of the membrane composition due to linoleic acid supply disturbed the basal enzymatic activity and Ser1177 phosphorylation of eNOS in a way that limited the role of histamine activation. Linoleic acid might involve the dysfunction of both eNOS basal activity and its phosphorylation status and may then contribute to an impaired vasodilatation in vivo. [source] Asymmetric dimethylarginine (ADMA): the silent transition from an ,uraemic toxin' to a global cardiovascular risk moleculeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2005D. Fliser Abstract Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l -arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process. [source] The alpha-amino group of l -arginine mediates its antioxidant effectEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2001S. Wallner Antioxidant effects may constitute part of the possible antiatherogenic effects of the amino acid l -arginine. These antioxidant properties were further characterized in a model of lipoprotein oxidation. Oxidation of lipoproteins in unfractionated human serum was continuously monitored by a fluorescent probe. The antioxidant effects of l -arginine, N -,-acetyl-arginine and vitamin E in combination with l -arginine were measured after initiation of free radical generation with either copper or 2,2,-azobis(2-amidinopropane) hydrochloride (AAPH). The half-time of the fast propagation rate for copper-induced lipoprotein oxidation increased after incubation with l -arginine in a dose-dependent manner (P < 0·01). N -,-acetyl-arginine did not show such effects. Vitamin E and l -arginine show different effects on copper-induced oxidation, the former increasing only lag-time, the latter increasing only propagation rate, and do not have reciprocal effects. In contrast to copper-induced oxidation, l -arginine increased the lag-time of AAPH-induced lipoprotein oxidation (P < 0·01), with no effect on the propagation rate at physiological concentrations. Again, N -,-acetyl-arginine did not show any antioxidant effects. Our experiments provide further evidence that mechanisms other than serving as a substrate for the NO-synthase could be involved in the antiatherosclerotic effect of l -arginine. In addition, our experiments clearly show, that the antioxidant effect of l -arginine is due to a chemical moiety different from that serving as the substrate for NO biosynthesis. [source] | |||||||||||||||||||||||||||||||||||||