Prader-Willi syndrome in a large sample from Spain: general features, obesity and regular use of psychotropic medication.

BACKGROUND: Prader-Willi syndrome (PWS), a genetically determined disorder, the most frequent cause of early onset obesity, is associated with physical and cognitive dysfunctions and behavioural disturbances; these disturbances are frequently treated with psychotropic medication. The aim of this cross-sectional study was to describe the characteristics of the first large national sample of persons with PWS in Spain and analyse the relationships of those characteristics with key demographic and clinical factors, particularly with obesity and the regular use of psychotropic medication. METHODS: Participants were recruited among all members of the Spanish Prader-Willi Association who agreed to take part in the study and fulfilled its inclusion criteria. Family and patient demographic features, family size and birth order, intelligence quotient (IQ), anthropometric measures, lifestyle habits, behavioural disturbances (with the Aberrant Behavior Checklist) and clinical data, as well as use of psychotropic drugs and their side effects (with the UKU scale), were collected in genetically confirmed cases of PWS. Bivariate and logistic regression analyses were used for determining the associations of demographic and clinical factors with both obesity and the regular use of psychotropic medication. RESULTS: The cohort included 177 participants (aged 6-48 years), that is, 90 (50.8%) males and 87 (49.2%) females. Behavioural disturbances were present in a range of 75% to 93% of participants; psychotropic medication was prescribed to 81 (45.8%) of them. Number of siblings showed a direct correlation with IQ, especially among males, and inappropriate speech was more intense in only-child females. Obesity was, in parallel, strongly associated with ascending age and with not being currently under growth hormone (GH) treatment. Participants taking any psychotropic medication were characterised by more frequent age ≥30 years, high level of hyperactivity and a psychiatric diagnosis. CONCLUSIONS: Characterisation of persons with PWS in Spain confirms their physical and behavioural phenotype and supports the long-term application of GH therapy and the rational use of psychotropic medication.

Incidence of recently acquired hepatitis C virus infection among HIV-infected patients in southern Spain.

OBJECTIVES: Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV. METHODS: Primary RAHC infection was diagnosed when anti-HCV antibody seroconversion was documented. In anti-HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected. RESULTS: All 350 patients tested negative for anti-HCV at baseline and had at least one follow-up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person-years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem-sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected. CONCLUSIONS: The incidence of RAHC among HIV-infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem-sex drugs among MSM.

Clinical, virological and phylogenetic characterization of a multiresistant HIV-1 strain outbreak in naive patients in southern Spain.

BACKGROUND: We describe the characteristics of an HIV-1 strain with six viral reverse transcriptase mutations (D67N, T69N/D, V118I, V179D, T215S and K219Q), which we have called the Malaga strain. This strain was detected in treatment-naive patients from southern Spain. METHODS: The study was undertaken at the Virgen de la Victoria Hospital, Malaga, a reference centre for the study of HIV-1 genotype resistance in Andalusia (the 'Costa del Sol'), Spain. Genotypic resistance testing was done in an automated sequencer. Phylogenetic analysis was performed using a 630 bp region of the reverse transcriptase with the mutations mentioned. RESULTS: Between 2007 and 2014, we detected the Malaga strain in 30 treatment-naive patients. All were MSM, seen at five hospitals on the Costa del Sol. In all cases, the HIV-1 was subtype B with viral tropism R5. Phylogenetic analysis based on the reverse transcriptase sequence showed consistent grouping (with a bootstrap value of the common node of 100%) of the isolates that shared the mutation pattern mentioned. This strain has not been detected elsewhere or in previously treated patients. All of the patients treated with first-line combination ART responded. CONCLUSIONS: We report a cluster of an HIV-1 strain with multiple resistance mutations that was transmitted over a period of >8 years, affecting 30 naive patients from the same geographical area. The strain was susceptible to first-line combination ART.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

A quantitative speciation model for the adsorption of organic pollutants on activated carbon.

Granular activated carbon (GAC) is commonly used as adsorbent in water treatment plants given its high capacity for retaining organic pollutants in aqueous phase. The current knowledge on GAC behaviour is essentially empirical, and no quantitative description of the chemical relationships between GAC surface groups and pollutants has been proposed. In this paper, we describe a quantitative model for the adsorption of atrazine onto GAC surface. The model is based on results of potentiometric titrations and three types of adsorption experiments which have been carried out in order to determine the nature and distribution of the functional groups on the GAC surface, and evaluate the adsorption characteristics of GAC towards atrazine. Potentiometric titrations have indicated the existence of at least two different families of chemical groups on the GAC surface, including phenolic- and benzoic-type surface groups. Adsorption experiments with atrazine have been satisfactorily modelled with the geochemical code PhreeqC, assuming that atrazine is sorbed onto the GAC surface in equilibrium (log Ks = 5.1 ± 0.5). Independent thermodynamic calculations suggest a possible adsorption of atrazine on a benzoic derivative. The present work opens a new approach for improving the adsorption capabilities of GAC towards organic pollutants by modifying its chemical properties.

Diversity of culturable halophilic archaea isolated from Rambla Salada, Murcia (Spain).

We have studied the diversity of culturable halophilic Archaea at Rambla Salada, Murcia (south-eastern Spain). We made 8 samplings at different places in this habitat during the years 2006 and 2007 and isolated a total of 49 strains, which were identified by means of phenotypic tests and the hypervariable V1-V3 region of the 16S rRNA gene sequences (around 500 bp). The ribosomal data showed that the isolates belonged to 12 genera within the Halobacteriaceae family, with Haloferax and Natrinema being the most abundant. Five strains showed less than 97% sequence identity with validly described species and may well represent new taxa. All the strains grew best with around 25% w/v salts, required high concentrations of NaCl and magnesium and produced red to pink colonies. They were facultative anaerobes with both respiratory and fermentative metabolisms. The diversity of the archaeal community was analysed with the MOTHUR package. We identified 14 OTUs at the 3% genetic distance level and found quite high diversity. Rarefaction curves of richness estimators and diversity indices demonstrated that our collection of isolates represented the archaeal community at Rambla Salada that can be isolated under the conditions used in this work. This is the first report to be published on the culturable archaea at Rambla Salada, an area of considerable ecological interest.

Role of Mycoplasma pneumoniae in pediatric encephalitis.

A retrospective study investigating all the infectious encephalitis cases hospitalized at the pediatric intensive care unit of Edouard Herriot University Hospital in Lyon, France, was carried out in order to estimate the prevalence of Mycoplasma pneumoniae in acute childhood encephalitis. From January 2001 to December 2005, the cases of 29 children were selected and reviewed. M. pneumoniae related encephalitis was considered as probable in five cases (17%) on the basis of positive serological tests or positive polymerase chain reaction (PCR) tests in throat or nasopharyngeal swab while the PCR tests performed from the cerebrospinal fluid were negative. This study suggests that M. pneumoniae may be a major cause of infectious encephalitis in children as well as enteroviruses or Epstein-Barr virus detected in five and three cases, respectively.

Degradation of tetradecyltrimethylammonium by Pseudomonas putida A ATCC 12633 restricted by accumulation of trimethylamine is alleviated by addition of Al 3+ ions.

AIMS: To establish if tetradecyltrimethylammonium (TDTMA) might be degraded by pure culture of Pseudomonas strains, and how the presence of a Lewis' acid in the medium influences its biodegradability. METHODS AND RESULTS: From different strains of Pseudomonas screened, only Pseudomonas putida A ATCC 12633 grows with 50 mg l(-1) of TDTMA as the sole carbon and nitrogen source. A monooxygenase activity catalyzed the initial step of the biodegradation. The trimethylamine (TMA) produced was used as nitrogen source or accumulated inside the cell. To decrease the intracellular TMA, the culture was divided, and 0.1 mmol l(-1) AlCl(3) added. In this way, the growth and TDTMA consumption increased. The internal concentration of TMA, determined using the fluorochrome Morin, decreased by the formation of Al(3+) : TMA complex. CONCLUSIONS: Pseudomonas putida utilized TDTMA as its sole carbon and nitrogen source. The TMA produced in the initial step of the biodegradation by a monooxygenase activity was used as nitrogen source or accumulated inside the cell, affecting the bacterial growth. This effect was alleviated by the addition of AlCl(3). SIGNIFICANCE AND IMPACT OF THE STUDY: The use of Lewis' acids to sequester intracellular amines offers an alternative to achieve an efficient utilization of TDTMA by Ps. putida.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis.

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽120 ng/mL versus 43% with concentration >120 ng/mL (P<0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾10(-3) and in those with MRD <10(-3) before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

[Knowledge level of hypertensive patients about hypertension. Relationship between knowledge level and hypertension control]. / Estudio Conocimiento: grado de conocimiento sobre hipertensión arterial de nuestros pacientes. Relación con el nivel de control de la misma.

OBJECTIVE: To assess the knowledge of the hypertensive patients about their hypertension and their relation to its control. MATERIAL AND METHODS: Cross-sectional study among 400 hypertensive patients, all over 18 years, selected from 50 primary-care centres, who responded to an hypertension-related survey. Included variables were survey items, age, gender, educational level, professional occupation, blood pressure data and antihypertensive treatment. The obtained differences were analyzed using the chi-square test, Kruskal-Wallis, Wilcoxon, Anova and Bonferroni methods. RESULTS: There were 323 valid surveys. 52.9% of respondents were women, the average age: 65.4 years (SD: 11.2), 54.8% of them had primary education. 39.6% were aware of the objectives of systolic BP control. Only 19.6% having knowledge of those for diastolic BP control, with no differences between controlled and uncontrolled (systolic BP: 39% vs 38.1%, P=.887; diastolic BP: 19.2% vs 21%, P=.721). Over 70% knew about lifestyle changes, without significant differences between controlled and uncontrolled respondents. 82% of controlled respondents, and 79% of those uncontrolled, recognized the chronical nature of the treatment (P=.548), but 15.1% of the controlled respondents and 12.4% of uncontrolled respondents did not see the relation between the treatment and hypertension control (P=.525). 31.1% believed to be well-controlled, but in fact was not. CONCLUSIONS: Our patients doesn't know blood pressure targets of control. There isn't relationship between this knowledge and control of hypertension.

Pseudomonas aeruginosa acid phosphatase. Activation by divalent cations and inhibition by aluminium ion.

In Pseudomonas aeruginosa, the effect of different cations on the acid phosphatase activity was studied in order to acquire more information related to a previously proposed mechanism, involving the coordinated action of this enzyme with phospholipase C. Although the natural substrate of this enzyme is phosphorylcholine, in order to avoid the possible interaction of its positive charge and those of the different cations with the enzyme molecule, the artificial substrate p-nitrophenylphosphate was utilized. Kinetic studies of the activation of acid phosphatase (phosphorylcholine phosphatase) mediated by divalent cations Mg2+, Zn2+ and Cu2+ revealed that all these ions bind to the enzyme in a compulsory order (ordered bireactant system). The Km values obtained for p-NPP in the presence of Mg2+, Zn2+ and Cu2+ were 1.4 mM, 1.0 mM and 3.5 mM, respectively. The KA values for the same ions were 1.25 mM, 0.05 mM and 0.03 mM, respectively. The Vmax obtained in the presence of Cu2+ was about twofold higher than that obtained in the presence of Mg2+ or Zn2+. The inhibition observed with Al3+ seems to be a multi-site inhibition. The K'app and n values, from the Hill plot, were about 0.25 mM and 4.0 mM, respectively, which were independent of the metal ion utilized as activator. It is proposed that the acid phosphatase may exert its action under physiological conditions, depending on the availability of either one of these metal ions.

Comparative uptake, retention and action of vincristine, vinblastine and vindesine on murine leukaemic lymphoblasts sensitive and resistant to vincristine.

1. The uptake and retention of vincristine (VCR), vinblastine (VBL) and vindesine (VDS) were evaluated comparatively with respect to their cytotoxic action on a murine lymphoblastic leukaemia (L5178Y). 2. The same parameters were measured on a derived subline of cells resistant to VCR (L5178Y/r) in order to determine whether the different degree of resistance to each alkaloid correlates with the amount of drug associated with the cells. 3. VCR was the most active on L5178Y cells (IC50 = 5.8 x 10(-9) M) while the activity of VBL and that of VDS were similar (IC50 4.4 x 10(-8) M and 3.5 x 10(-8) M, respectively). Nevertheless, a considerably larger amount of VBL was taken up by the cells compared to VDS, although there were no significant differences in their cytotoxic action. 4. The VCR resistant cell line also expressed resistance to VDS, whose IC50 was increased by a factor of 11.4, but not to VBL. However, the uptake and retention of the three alkaloids were similarly reduced in L5178Y/r cells regardless of the degree of resistance expressed. 5. Although a decreased drug uptake and/or retention by the cells provides an explanation for the resistance to vinca alkaloids, they do not seem to be the only factors accounting for the resistance shown by the cell line which we have isolated. 6. The results seem to indicate that part of the VBL taken up by the cells is not used to induce the cytotoxic effect, but is diverted to some cellular compartment(s) or rate controlling process(es) which are different from the target that mediates its cytotoxic action.

Inhibition of neuroeffector transmission in human vas deferens by sildenafil.

Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 microM) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 microM) and zaprinast (100 microM). ODQ (10 microM) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca(2+)-activated K(+) channels.

Neurogenic contraction and relaxation of human penile deep dorsal vein.

1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.

Chloral hydrate inhibition in vitro of ATPase in membrane of rat erythrocytes and in microsomes of dog kidney external medulla.

The study of the general anesthetic chloral hydrate and its effects on rat erythrocyte membranes and dog kidney microsomes showed that ATPases were reversibly inhibited in every case. The inhibition was cooperative in the cases of (Mg2+ + Na+ + K+)-ATPase, Mg2+-ATPase and (Na+ + K+)-ATPase of rat erythrocyte membrane, while Ca2+-ATPase and (Mg2+ + Ca2+)-ATPase were non-cooperative. The chloral hydrate concentrations necessary to diminish the activity of the enzyme to half of the Vmax (I50) were 6 mM for Ca2+-ATPase from erythrocyte membranes and 82 mM for Mg2+-ATPase from intact external kidney medulla microsomes. When Ca2+-ATPase was studied in the absence of Mg2+ in these microsomes, the affinity for Ca2+ was very low, but the enzyme was sensitive to chloral hydrate.

Inhibition of nitric oxide activity by arginine analogs in human renal arteries.

BACKGROUND: Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study we tested the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries. METHODS: Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ baths for isometric recording of tension. We then studied the effects of N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine [ADMA]), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated conditions. RESULTS: In precontracted arteries, L-NMMA (1 micromol/L to 1 mmol/L) and ADMA (1 micromol/L to 3 mmol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC50] = 13.3 micromol/L and 17.5 micromol/L, respectively; Emax = 15+/-4% and 17+/-4% of the response to 100 mmol/L KCl, respectively). Aminoguanidine (0.01 to 3 mmol/L) and MG (0.01 to 3 mmol/L) produced endothelium-independent contractions (Emax = 9+/-3% and 16+/-2% of the response to 100 mmol/L KCl, respectively). L-arginine (1 mmol/L) but not D-arginine (1 mmol/L) prevented the contractions by L-NMMA and ADMA, but did not change contractions induced by AG and MG. In precontracted arteries, the relaxation to acetylcholine was decreased but not abolished by L-NMMA and ADMA. The remaining relaxation was reduced by charybdotoxin (0.1 mol/L) and tetraethylammonium (1 mmol/L). CONCLUSIONS: The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries.