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1.
Int Heart J ; 61(5): 984-992, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921665

RESUMO

Uric acid is generated with reactive oxygen species via xanthine oxidase (XO), and hyperuricemia, which is identified as the excess of uric acid in the blood, has been associated with vascular endothelial dysfunction. However, the effects of urate-lowering medicines on endothelial function have not been fully elucidated. Thus this study determined and compared the effects of benzbromarone (urate transporter 1 inhibitor) and febuxostat (XO inhibitor) on endothelial function.This randomized, cross-over, open-label study initially recruited 30 patients with hyperuricemia. They were divided into two groups, treated initially with benzbromarone or febuxostat for three months and then were switched for the next three months. Endothelial function was defined as reactive hyperemia indexes (RHI) determined using Endo-PAT 2000 before and at three and six months after medication using the two agents. Blood levels of asymmetric dimethylarginine (ADMA) and high-molecular-weight (HMW) adiponectin were also compared. We finally analyzed data from 24 patients whose endothelial function was assessed as described above.Our findings show that levels of uric acid significantly decreased, whereas those of HMW adiponectin and the RHI have significantly increased after treatment with benzbromarone. Meanwhile, in patients administered with febuxostat, uric acid levels tended to decrease and RHI significantly decreased. Neither of the two agents altered ADMA levels. The changes in RHI (P = 0.026) and HMW adiponectin levels (P = 0.001) were found to be significantly greater in patients treated with benzbromarone than febuxostat. Changes in the levels of HMW adiponectin and of uric acid were significantly correlated (r = -0.424, P = 0.039).Benzbromarone has increased adiponectin besides reducing uric acid levels, and thus, this might confer more benefits on endothelial function than febuxostat.


Assuntos
Benzobromarona/uso terapêutico , Endotélio Vascular/fisiopatologia , Febuxostat/uso terapêutico , Hiperemia/fisiopatologia , Hiperuricemia/tratamento farmacológico , Uricosúricos/uso terapêutico , Adiponectina/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Estudos Cross-Over , Feminino , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Resultado do Tratamento , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores
2.
PLoS One ; 15(6): e0235095, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589680

RESUMO

Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization. We measured plasma enrichments via liquid chromatography tandem mass spectrometry (LC-MS/MS) and body compostion by echo-MRI. WBP, clearance rates, and de novo ARG and NO were calculated. Compared to LA mice, HA mice had lower plasma concentrations of GLU (71.1%; 36.8 ± 2.9 vs. 17.5 ± 1.7µM; p<0.0001), CIT (21%; 57.3 ± 2.3 vs. 46.4 ± 1.5µM; p = 0.0003), and ORN (40.1%; 55.4 ± 7.3 vs. 36.9 ± 2.6µM; p = 0.0241), but no differences for GLN, PHE, and ARG. However, HA mice had higher estimated NO production ratio (0.64 ± 0.08; p = 0.0197), higher WBP for CIT (21.8%, 8.6 ± 0.2 vs. 10.7 ± 0.3 nmol/g-lbm/min; p<0.0001), ARG (21.4%, 35.0 ± 0.6 vs. 43.4 ± 0.7 nmol/g-lbm/min; p<0.0001), PHE (7.6%, 23.8 ± 0.5 vs. 25.6 ± 0.5 nmol/g-lbm/min; p<0.0100), and lower GLU (78.5%; 9.4 ± 1.1 vs. 4.1 ± 1.6 nmol/g lbm/min; p = 0.0161). We observed no significant differences in WBP for GLN, ORN, PHE, or de novo ARG. We concluded that HA mice have an activated whole-body ARG pathway, which may be associated with regulating PA levels via increased NO production.


Assuntos
Arginina/sangue , Atividade Motora , Óxido Nítrico/sangue , Animais , Cromatografia Líquida/métodos , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Condicionamento Físico Animal , Espectrometria de Massas em Tandem/métodos
3.
Clin Chem Lab Med ; 58(7): 1100-1105, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32573995

RESUMO

Background Comprehensive information has been published on laboratory tests which may predict worse outcome in Asian populations with coronavirus disease 2019 (COVID-19). The aim of this study is to describe laboratory findings in a group of Italian COVID-19 patients in the area of Valcamonica, and correlate abnormalities with disease severity. Methods The final study population consisted of 144 patients diagnosed with COVID-19 (70 who died during hospital stay and 74 who survived and could be discharged) between March 1 and 30, 2020, in Valcamonica Hospital. Demographical, clinical and laboratory data were collected upon hospital admission and were then correlated with outcome (i.e. in-hospital death vs. discharge). Results Compared to patients who could be finally discharged, those who died during hospital stay displayed significantly higher values of serum glucose, aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), urea, creatinine, high-sensitivity cardiac troponin I (hscTnI), prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (APTT), D-dimer, C reactive protein (CRP), ferritin and leukocytes (especially neutrophils), whilst values of albumin, hemoglobin and lymphocytes were significantly decreased. In multiple regression analysis, LDH, CRP, neutrophils, lymphocytes, albumin, APTT and age remained significant predictors of in-hospital death. A regression model incorporating these variables explained 80% of overall variance of in-hospital death. Conclusions The most important laboratory abnormalities described here in a subset of European COVID-19 patients residing in Valcamonica are highly predictive of in-hospital death and may be useful for guiding risk assessment and clinical decision-making.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , Glicemia/análise , Proteína C-Reativa/análise , Carnosina/sangue , Técnicas de Laboratório Clínico , Comorbidade , Infecções por Coronavirus/fisiopatologia , Creatina Quinase/sangue , Creatinina/sangue , Combinação de Medicamentos , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio , Mortalidade Hospitalar , Humanos , Itália , L-Lactato Desidrogenase/sangue , Leucócitos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Pandemias , Tempo de Tromboplastina Parcial , Pneumonia Viral/fisiopatologia , Tempo de Protrombina , Albumina Sérica Humana/análise , Troponina I/sangue , Ureia/sangue
4.
PLoS One ; 15(4): e0231633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353864

RESUMO

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.


Assuntos
Antineoplásicos/uso terapêutico , Arginina/metabolismo , Carcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Desiminases de Arginina em Proteínas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Arginina/sangue , Arginina/deficiência , Argininossuccinato Sintase/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ligação Proteica , Desiminases de Arginina em Proteínas/administração & dosagem , Desiminases de Arginina em Proteínas/metabolismo , Ratos , Albumina Sérica/metabolismo
5.
J Anim Sci ; 98(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32152623

RESUMO

Creatine stores high-energy phosphate bonds in muscle, which is critical for muscle activity. In animals, creatine is synthesized in the liver from guanidinoacetic acid (GAA) with methylation by S-adenosylmethionine. Because methyl groups are used for the conversion of GAA to creatine, methyl group deficiency may occur as a result of GAA supplementation. With this study, the metabolic responses of cattle to post-ruminal supplementation of GAA were evaluated with and without methionine (Met) supplementation as a source of methyl groups. Six ruminally cannulated Holstein heifers (520 kg) were used in a split-plot design with treatments arranged as a 2 × 5 factorial. The main plot treatments were 0 or 12 g/d of l-Met arranged in a completely randomized design; three heifers received each main plot treatment throughout the entire experiment. Subplot treatments were 0, 10, 20, 30, and 40 g/d of GAA, with GAA treatments provided in sequence from lowest to highest over five 6-d periods. Treatments were infused continuously to the abomasum. Heifers were limit-fed twice daily a diet consisting of (dry matter basis) 5.3 kg/d rolled corn, 3.6 kg/d alfalfa hay, and 50 g/d trace-mineralized salt. Plasma Met increased (P < 0.01) when Met was supplemented, but it was not affected by supplemental GAA. Supplementing GAA linearly increased plasma arginine (% of total amino acids) and plasma concentrations of GAA and creatinine (P < 0.001). Plasma creatine was increased at all levels of GAA except when 40 g/d of GAA was supplemented with no Met (GAA-quadratic × Met, P = 0.07). Plasma homocysteine was not affected by GAA supplementation when heifers received 12 g/d Met, but it was increased when 30 or 40 g/d of GAA was supplemented without Met (GAA-linear × Met, P = 0.003); increases were modest and did not suggest a dangerous hyperhomocysteinemia. Urinary concentrations of GAA and creatine were increased by all levels of GAA when 12 g/d Met was supplemented; increasing GAA supplementation up to 30 g/d without Met increased urinary GAA and creatine concentrations, but 40 g/d GAA did not affect urine concentrations of GAA and creatine when no Met was supplemented. Overall, post-ruminal GAA supplementation increased creatine supply to cattle. A methyl group deficiency, demonstrated by modest increases in plasma homocysteine, became apparent when 30 or 40 g/d of GAA was supplemented, but it was ameliorated by 12 g/d Met.


Assuntos
Bovinos/metabolismo , Creatina/metabolismo , Suplementos Nutricionais/análise , Glicina/análogos & derivados , Homocisteína/sangue , Metionina/farmacologia , Abomaso/metabolismo , Ração Animal/análise , Animais , Arginina/sangue , Bovinos/sangue , Dieta/veterinária , Feminino , Glicina/farmacologia , Medicago sativa , Distribuição Aleatória , Zea mays
6.
Phytother Res ; 34(8): 2023-2031, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32144833

RESUMO

The present study sought to investigate the effect of micronized resveratrol supplementation on serum levels of asymmetric de-methyl-arginine (ADMA) and paraoxonase-1 (PON1) activity in patients with type 2 diabetes (T2D). In this double-blinded randomized trial, 76 patients with T2D were recruited. Participants were randomly assigned to consume 1,000 mg resveratrol or placebo capsules (methylcellulose) per day, for 8 weeks. Serum levels of ADMA and PON1 enzyme activity were measured at the beginning and end of the intervention using the enzyme-linked immunosorbent assay method. In total, 71 participants completed the study. Our results showed that resveratrol significantly decreased serum levels of ADMA (-0.16 ± 0.11, p < .001) and improved PON1 enzyme activity (15.39 ± 13.99, p < .001) compared with placebo, after adjusting for confounding factors (age, sex, and baseline body mass index). Our findings suggest that 8-week resveratrol supplementation may produce beneficial effects on serum levels of ADMA and PON1 enzyme activity in patients with T2DM. However, further research is needed to confirm the veracity of these results.


Assuntos
Arginina/sangue , Arildialquilfosfatase/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resveratrol/química , Adulto , Arginina/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resveratrol/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-32062367

RESUMO

Protein-arginine methyltransferases catalyze the methylation of the guanidine (NG) group of proteinic L-arginine (Arg) to produce monomethyl and dimethylarginine proteins. Their proteolysis releases the free amino acids monomethylarginine (MMA), symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA), respectively. MMA, SDMA and ADMA are inhibitors of the nitric oxide synthase (NOS) activity. High circulating and low urinary concentrations of ADMA and SDMA are considered risk factors in the cardiovascular and renal systems, mainly due to their inhibitory action on NOS activity. Identity, biological activity and concentration of NG-methylated proteins are largely unknown. The present study addressed these issues by using GC-MS and LC-MS/MS approaches. GC-MS was used to quantify free ADMA released by classical HCl-catalyzed hydrolysis of three synthetic Arg-vasopressin (V) peptides and of unknown endogenous NG-dimethylated proteins. The cyclic (c) disulfide forms of Arg-vasopressin analogs, i.e., Arg-vasopressin (cV-Arg-Gly-NH2), asymmetrically NG-dimethylated vasopressin (cV-ADMA-Gly-NH2) and symmetrically NG-dimethylated vasopressin (cV-SDMA-Gly-NH2) were used as model peptides in quantitative GC-MS analyses of ADMA, SDMA and other expected amino acids from the hydrolyzed Arg-vasopressin analogs. cV-ADMA-Gly-NH2 and cV-SDMA-Gly-NH2 were discriminated from cV-Arg-Gly-NH2 by LC-MS and LC-MS/MS, yet they were indistinguishable from each other. The same applies to the respective open (o) reduced and di-S-acetamide forms of oV-ADMA-Gly-NH2, oV-SDMA-Gly-NH2 and oV-Arg-Gly-NH2. Our LC-MS and LC-MS/MS studies suggest that the Arg-vasopressin analogs form [(M-H)]+ and [(M-H)+H]+ in the positive ESI mode and undergo in part conversion of their terminal Gly-NH2 (NH2, 16 Da) group to Gly-OH (OH, 17 Da). The product ion mass spectra of the di-S-acetamide forms are complex and contain several intense mass fragments differing by 1 Da. cV-ADMA-Gly-NH2 and cV-SDMA-Gly-NH2 induced platelet aggregation in platelet-rich human plasma with moderately different initial velocity and maximal aggregation rates compared to cV-Arg-Gly-NH2. Previous studies showed that human red blood cells are rich in large (>50 kDa) ADMA-containing proteins of unknown identity. Our LC-MS/MS proteomic study identified several membrane and cytosolic erythrocytic NG-dimethylated proteins, including spectrin-α (280 kDa), spectrin-ß (247 kDa) and protein 4.1 (80 kDa). Being responsible for the stability of the erythrocyte membrane, the newly identified main targets for NG-dimethylation in human erythrocytes should be given a closer look in erythrocytic diseases like hereditary spherocytosis.


Assuntos
Arginina Vasopressina , Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Guanidina/química , Espectrometria de Massas em Tandem/métodos , Arginina/análogos & derivados , Arginina/análise , Arginina/sangue , Arginina/química , Arginina Vasopressina/análise , Arginina Vasopressina/sangue , Arginina Vasopressina/química , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/química , Humanos , Modelos Lineares , Masculino , Peptídeos/análise , Peptídeos/sangue , Peptídeos/química , Projetos Piloto , Processamento de Proteína Pós-Traducional
8.
Adv Clin Exp Med ; 29(1): 63-70, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31967743

RESUMO

BACKGROUND: The most commonly recognized cardiovascular risk factors (CVRF) include smoking cigarettes, manifestation of arterial hypertension (AH), hypercholesterolemia, hypertriglyceridemia, manifestation of type 2 diabetes mellitus (DM), and the presence of overweight or obesity. In recent years, investigations have documented the significance of asymmetric dimethylarginine concentration (ADMA) in the pathogenesis of diseases affecting the cardiovascular system. OBJECTIVES: To evaluate the relationship between the number of CVRF and blood ADMA concentration. MATERIAL AND METHODS: The study was conducted on a sample of 138 individuals (mean age 54.90 ±10.38 years). Among the participants, we distniguished subgroups with no CVRF (group A, n = 21), with 1-2 CVRF (group B, n = 53), with 3-4 CVRF (group C, n = 55), and with 5-6 CVRF (group D, n = 9). Plasma concentrations of arginine and of endogenous methylarginines were estimated. RESULTS: Plasma ADMA concentrations proved to be significantly higher in groups B, C and D than those in group A. Regression analysis allowed us to demonstrate that in the studied population of patients, manifestation of type 2 DM, followed by AH and hypercholesterolemia, were linked to the highest probability of elevated plasma ADMA concentration. CONCLUSIONS: Higher concentration of ADMA in the blood may be a marker for higher cardiovascular risk, especially associated with hypertension, type 2 DM and hypercholesterolemia.


Assuntos
Arginina/análogos & derivados , Biomarcadores , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Idoso , Arginina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Humanos , Pessoa de Meia-Idade , Fatores de Risco
9.
PLoS One ; 15(1): e0227964, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990929

RESUMO

Hyperthyroidism in cats can mask changes in renal function, including chronic kidney disease (CKD), because of hyperfiltration and muscle loss. Symmetric dimethylarginine (SDMA) has been shown to increase earlier than creatinine in cats with renal dysfunction, and, unlike creatinine, SDMA is not impacted by lean muscle mass. The aim of this study was to describe the relationship between SDMA, creatinine, body weight and TT4 over time during treatment of hyperthyroidism. Cats were retrospectively identified from the US IDEXX Reference Laboratories database where TT4, SDMA and creatinine were measured on the same cat at multiple time points. A hyperthyroid treated group was identified (TT4 ≤ 4.7 µg/dL and decreased by a minimum of 2.5 µg/dL) that had body weight and laboratory results available from more than one visit, and was used to evaluate body weight, creatinine, SDMA and TT4 pre-treatment and at 1-30, 31-60, 61-90, 91-120 days post-treatment. Creatinine significantly decreased with increasing concentrations of TT4 (Spearman's ρ = -0.37, P < 0.001), whereas SDMA did not. Body weight, SDMA and creatinine concentrations significantly increased during the immediate 1-30 day post-treatment period (P < 0.012, P < 0.001, P < 0.001, respectively). During treatment creatinine continued to increase as cats gained weight. In contrast, SDMA remained stable during treatment and was comparable to age-matched control cats. Therefore, SDMA may be a more reliable biomarker of renal function than creatinine in hyperthyroid cats before and during treatment.


Assuntos
Arginina/análogos & derivados , Creatinina/sangue , Hipertireoidismo/sangue , Insuficiência Renal Crônica/sangue , Animais , Arginina/sangue , Biomarcadores/sangue , Peso Corporal/fisiologia , Gatos , Testes Diagnósticos de Rotina , Feminino , Taxa de Filtração Glomerular/fisiologia , Hipertireoidismo/patologia , Hipertireoidismo/veterinária , Rim/metabolismo , Rim/patologia , Masculino , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/veterinária , Estudos Retrospectivos
10.
J Vet Med Sci ; 82(3): 307-313, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31932535

RESUMO

D-Amino acids exert various physiological functions and are widely present in animals. However, they are absorbed to a lesser extent than L-amino acids. Little is known about D-arginine (D-Arg); however, its isomer L-Arg serves as a substrate for several metabolites and exhibits various functions including promotion of growth hormone secretion. Milk is the only nutrient source for infants; it plays an important role during their initial growth and brain development. No studies have evaluated the availability of D-Arg in the brain and milk in mammals. Here, we have studied the differential availability of orally administered D- and L-Arg in the brain and milk using ICR mice. Our results revealed that without D-Arg administration, D-Arg was undetectable in both plasma and brain samples. However, the plasma D-Arg was about twice the concentration of L-Arg post administration of the same. In the cerebral cortex and hypothalamus, L-Arg concentration remained almost constant for over period of 90 min after L-Arg treatment. Nevertheless, the L-Arg concentration decreased after D-Arg administration with time compared to the case post L-Arg administration. Contrastingly, D-Arg level sharply increased at both the brain regions with time after D-Arg treatment. Furthermore, L-Arg concentration in the milk hardly increased after L-Arg administration. Interestingly, oral administration of D-Arg showed efficient enrichment of D-Arg in milk, compared with L-Arg. Thus, our results imply that D-Arg may be available for brain development and infant nourishment through milk as an oral drug and/or nutrient supplement.


Assuntos
Arginina/química , Química Encefálica , Leite/química , Administração Oral , Animais , Arginina/administração & dosagem , Arginina/sangue , Feminino , Masculino , Camundongos Endogâmicos ICR , Estereoisomerismo
11.
Life Sci ; 242: 116931, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31618610

RESUMO

AIMS: With the improvement of the survival rates in children acute lymphoblastic leukemia (ALL), some children ALL survivors show impaired cognitive function. Methotrexate (MTX), an essential component in ALL treatment, has been reported to be related to neurologic sequelae and to increased oxidative stress through its interactions with enzymes in the folate pathway. Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric oxide synthase, and increased ADMA may result from increased oxidants. Melatonin is an antioxidant; however, its role in MTX neuropathy is not well studied. We developed a rat model mimicking child ALL treatment to explore peripheral and central homocysteine and ADMA regulation after MTX and found potential treatment choice. MAIN METHODS: Preweaning male Sprague-Dawley rats were used in this study. Experiment 1 evaluated spatial performance in rats with intrathecal (IT) MTX, intraperitoneal (IP) MTX, or combined IT and IP MTX, protocols mimicking ALL treatment in children. Experiment 2 focused on rats with combined IT and IP MTX, evaluating spatial performance and plasma and dorsal hippocampal homocysteine and ADMA levels, their regulation, and the protective effect of melatonin. KEY FINDINGS: Combined IT and IP MTX treatment caused in spatial deficits in developing rats, and melatonin restored the spatial performance. Alterations in peripheral and central homocysteine and ADMA concentrations and their regulation were found and could be alleviated by melatonin treatment. SIGNIFICANCES: Combined IP and IT MTX treatment caused spatial deficits in developing rats. Melatonin could restore spatial performance through alleviating the effects on the imbalance of oxidative stress.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Arginina/análogos & derivados , Hipocampo/química , Hiper-Homocisteinemia/induzido quimicamente , Melatonina/farmacologia , Metotrexato/efeitos adversos , Comportamento Espacial/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Arginina/análise , Arginina/sangue , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Metotrexato/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
12.
Vet Parasitol ; 277: 109015, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31874403

RESUMO

Canine leishmaniosis (CanL)-associated chronic kidney disease is a leading cause of morbidity and mortality in Mediterranean countries. Novel renal biomarkers, such as serum symmetric dimethylarginine (sSDMA), may be useful surrogates for the detection of renal functional impairment. The objectives of this study were to investigate sSDMA concentrations in dogs with CanL, with and without azotemia, and to establish any potential association with the prevalence and severity of proteinuria, with the prevalence of decreased urine specific gravity and with the LeishVet clinical stages of CanL. Serum samples from 68 dogs with CanL (50 nonazotemic and 18 azotemic) and 17 healthy dogs were retrospectively examined. Increased sSDMA was documented in 26 % of dogs with CanL without azotemia and in 83.3 % of dogs with azotemia. Serum SDMA was significantly higher in azotemic compared to nonazotemic dogs and was associated with the presence and severity of proteinuria, the decreased urine specific gravity and the advanced clinical stages of CanL. The results of the present study indicate that sSDMA may be a useful adjunct to serum creatinine and urine protein/creatinine ratio for the detection of CanL-associated nephropathy, but it is of limited value for distinguishing among the LeishVet clinical stages of CanL.


Assuntos
Arginina/análogos & derivados , Doenças do Cão/diagnóstico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Insuficiência Renal Crônica/etiologia , Animais , Arginina/sangue , Azotemia/veterinária , Biomarcadores/sangue , Doenças do Cão/sangue , Cães , Leishmania infantum/fisiologia , Insuficiência Renal Crônica/sangue , Estudos Retrospectivos
13.
J Infect Dis ; 221(1): 127-137, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31693729

RESUMO

BACKGROUND: In severe falciparum malaria, unlike sepsis, hypotension on admission is uncommon. We hypothesized that low nitric oxide bioavailability due to the presence of cell-free hemoglobin (CFH) increases vascular tone in severe malaria. METHODS: Patients with severe malaria (n = 119), uncomplicated malaria (n = 91), or suspected bacterial sepsis (n = 56), as well as healthy participants (n = 50), were recruited. The systemic vascular resistance index (SVRI) was estimated from the echocardiographic cardiac index and the mean arterial pressure. RESULTS: SVRI and hematocrit levels were lower and plasma CFH and asymmetric dimethylarginine levels were higher in patients with malaria, compared with healthy participants. In multivariate linear regression models for mean arterial pressure or SVRI in patients with severe malaria, hematocrit and CFH but not asymmetric dimethylarginine were significant predictors. The SVRI was lower in patients with suspected bacterial sepsis than in those with severe malaria, after adjustment for hematocrit and age. Plasma CFH levels correlated positively with the core-peripheral temperature gradient and plasma lactate levels and inversely with the perfusion index. Impaired peripheral perfusion, as reflected by a low perfusion index or a high core-peripheral temperature gradient, predicted mortality in patients with severe malaria. CONCLUSIONS: CFH is associated with mean arterial pressure, SVRI, and peripheral perfusion in patients with severe malaria. This may be mediated through the nitric oxide scavenging potency of CFH, increasing basal vascular tone and impairing tissue perfusion.


Assuntos
Pressão Arterial , Hemoglobinas/metabolismo , Malária Falciparum/fisiopatologia , Fluxo Sanguíneo Regional , Resistência Vascular , Adulto , Arginina/análogos & derivados , Arginina/sangue , Bacteriemia/fisiopatologia , Estudos de Casos e Controles , Ecocardiografia , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico , Gravidade do Paciente , Adulto Jovem
14.
Immunity ; 51(6): 1074-1087.e9, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31784108

RESUMO

Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8+ T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation. VIDEO ABSTRACT.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon Tipo I/imunologia , Fígado/metabolismo , Vírus da Coriomeningite Linfocítica/imunologia , Receptor de Interferon alfa e beta/metabolismo , Animais , Arginina/sangue , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Feminino , Hepatócitos/metabolismo , Fígado/imunologia , Fígado/virologia , Coriomeningite Linfocítica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ornitina/sangue , Ornitina Carbamoiltransferase/genética , Transdução de Sinais/imunologia , Ureia/metabolismo , Células Vero
15.
BMC Geriatr ; 19(1): 370, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870320

RESUMO

BACKGROUND: Reduced glomerular filtration rate and increased asymmetric dimethylarginine (ADMA) are prevalent in elderly people. However, most of the studies that have examined the association between the two conditions were performed in patients with renal dysfunction, but not in the general elderly population. Thus, we investigated an association between estimated glomerular filtration rate (eGFR) and ADMA concentration among community-dwelling older Koreans. METHODS: A cross-sectional study was conducted on 269 men and 382 women (mean age, 71.6 years) enrolled in the Korean Social Life, Health, and Aging Project (KSHAP), a population-based cohort study of health determinants in elderly Koreans. We calculated eGFR using chronic kidney disease- Epidemiology Collaboration Group (CKD-EPI) equation. ADMA concentration was measured by an enzyme-linked immunosorbent assay. The association between eGFR and ADMA concentrations was analyzed by multiple linear regression models. RESULTS: The mean ADMA was significantly higher in people with eGFR< 60 mL/min/1.73m2 (0.691 µmol/L) than in those with eGFR≥60 mL/min/1.73m2 (0.667 µmol/L, p = 0.013). The negative correlations between eGFR level and ADMA concentrations were significant in men and women after adjusted age. After adjusting for potential confounders which were sex, age, body surface, blood pressure, total and HDL cholesterol, diabetes, smoking, and drinking, eGFR levels were inversely associated with ADMA concentrations both in men (ß = - 0.0015, p = 0.005) and women (ß = - 0.001, p = 0.039). CONCLUSION: Our findings suggest that an inverse association exists between eGFR and ADMA concentrations among the Korean elderly in a rural community.


Assuntos
Arginina/análogos & derivados , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , População Rural , Idoso , Arginina/sangue , Biomarcadores/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , República da Coreia/epidemiologia
16.
J Pak Med Assoc ; 69(12): 1808-1811, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31853108

RESUMO

OBJECTIVE: To compare serum levels of asymmetric dimethylarginine between premenopausal and postmenopausal women, and to evaluate its relationship with time since onset of menopause. METHODS: The cross-sectional comparative study was conducted at Islamic International Medical College, Rawalpindi, Pakistan, from April 2017 to March 2018, and comprised individuals recruited from the Gynaecology and Obstetrics outpatient department of the Pakistan Railway Hospital in the city. The subjects were divided into two groups; pre-menopausal women in Group I and postmenopausal in Group II. Group II was subdivided into three categories according to time since onset of menopause. Serum asymmetric dimethylarginine levels were estimated in each subject. Data was analysed using SPSS 21. RESULTS: Of the 80 subjects, there were 40(50%) in Group I with a mean age of 36.25}6.8 years, 40(50%) in Group II with a mean age of49.83}4.35 years. There was a significant increase in mean asymmetric dimethylarginine levels in Group II compared to Group I (p<0.05). There was also a significant increase in asymmetric dimethylarginine levels with increase in duration since the onset of menopause (p<0.001). CONCLUSIONS: Levels of asymmetric dimethylarginine increased significantly after menopause.


Assuntos
Arginina/análogos & derivados , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Adulto , Arginina/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Paquistão/epidemiologia
17.
Nutrients ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694176

RESUMO

Chemotherapy for colorectal cancer may lower muscle protein synthesis and increase oxidative stress. We hypothesize that chemotherapy may worsen plasma amino acids (AAs) and markers of oxidative stress (MOS). Therefore, this study aimed to document plasma AAs and MOS before, during and after chemotherapy in colorectal cancer (CRC) surgery patients. Fourteen normal-weight CRC patients were enrolled one month after surgery and scheduled for oxaliplatin-fluoropyrimidine combination (XELOX) therapy. Venous blood samples for AA and MOS (malondialdehyde, MDA; 8-hydroxy-2'-deoxyguanosine, 8-OHdG) measurements were drawn in fasting patients before each oxaliplatin infusion at initiation (A), 1 month (B) and 3 months (C) of the therapy, and after XELOX had finished (6 months, D). The results showed that during XELOX therapy (from phase B to phase D), in comparison to baseline (phase A), the branched chain amino acid/essential amino acid ratio, branched chain amino acids expressed as a percentage of total AAs, and arginine expressed as a percentage of total AAs significantly decreased (p = 0.017, p = 0.028, p = 0.028, respectively). Plasma levels of MOS did not change significantly. This study indicates that XELOX therapy does not affect plasma AA levels or worsen oxidative stress.


Assuntos
Aminoácidos/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Capecitabina/farmacologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Oxaloacetatos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/sangue , Arginina/sangue , Colectomia , Neoplasias Colorretais/cirurgia , Jejum/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Operatório , Estudos Prospectivos
18.
Medicina (Kaunas) ; 55(11)2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31671882

RESUMO

Background and Objectives: Vasovagal syncope (VVS) is the most common cause of syncope and has multiple pathophysiological mechanisms. Asymmetric dimethylarginine (ADMA) is the major inhibitor of nitric oxide (NO). In this study, we aimed to investigate the relationship between plasma ADMA levels and syncope during the head-up tilt (HUT) test. Materials and Methods: Overall, 97 patients were included in this study. They were above 18 years of age and were admitted to our clinic with the complaint of at least one episode of syncope consistent with VVS. The HUT test was performed in all patients. Patients were divided into the following two groups based on the HUT test results: group 1 included 57 patients with a positive HUT test and group 2 included 35 patients with a negative HUT test. Blood samples were taken before and immediately after the HUT test to measure ADMA levels. Results: No significant intergroup differences were observed concerning gender and age (female gender 68% vs 60%; mean age 24.85 ± 4.01 vs 25.62 ± 3.54 years, respectively, for groups 1 and 2). ADMA values were similar between groups 1 and 2 before the HUT test [ADMA of 958 (544-1418) vs 951 (519-1269); p = 0.794]. In the negative HUT group, no significant differences were observed in ADMA levels before and after the HUT test [ADMA of 951 (519-1269) vs 951 (519-1566); p = 0.764]. However, in the positive HUT group, ADMA levels were significantly decreased following the HUT test [pretest ADMA of 958 (544-1418) vs post-test ADMA of 115 (67-198); p < 0.001]. Conclusion: ADMA levels significantly decreased after the HUT test in patients with VVS.


Assuntos
Arginina/análogos & derivados , Síncope Vasovagal/sangue , Adolescente , Adulto , Arginina/análise , Arginina/sangue , Feminino , Humanos , Masculino , Estudos Prospectivos , Estatísticas não Paramétricas , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/fisiopatologia , Turquia
19.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625365

RESUMO

BACKGROUND: Workers can be exposed to cadmium (Cd) in various industries. On the other hand, another potential source for Cd exposure is the food chain and smoking. Environmental pollution to Cd plays an important role in the development of atherosclerosis. Asymmetric dimethyl arginine (ADMA) levels promote the development of endothelial dysfunction and atherosclerosis-related diseases such as hypertension, acute coronary syndrome, congestive heart failure, and peripheral vascular diseases. The aim of this study is to evaluate the cardiovascular risks of non-symptomatic cadmium-exposed workers and to promote the value of methylated arginines in screening of toxic exposures. METHODS: A total 176 participants were included in the study which has been separated as control group (n = 79) and Cd-exposed group (n = 94). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for toxicological analysis of Cd levels. Also, liquid Chromatography-Mass Spectrometry (LC-MS/MS) was used for levels of methylated arginines such as ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl-L-arginine (L-NM-MA), homoarginine, and citrulline. RESULTS: Statistically significant differences were observed for control and Cd-exposed groups, respectively as follows: Cd levels (0.25 ± 0.13 µg/L and 1.33 ± 0.61 µg/L), ADMA (0.16 ± 0.04 µmol/L and 0.22 ± 0.11 µmol/L), SDMA (0.21 ± 0.06 µmol/L and 0.27 ± 0.07 µmol/L), L-NMMA(0.02 ± 0.01 µmol/L and 0.03 ± 0.01µmol/L), and arginine/ADMA levels (695.82 ± 620.63 and 478.30 ± 432.61). CONCLUSIONS: Our results suggest that workers chronically exposed to Cd showed imbalances in endothelial parameters.


Assuntos
Arginina/análogos & derivados , Arginina/sangue , Cádmio/análise , Endotélio Vascular/fisiopatologia , Poluentes Ambientais/análise , Hipertensão/sangue , Adulto , Aterosclerose/sangue , Aterosclerose/induzido quimicamente , Aterosclerose/fisiopatologia , Cromatografia Líquida , Poluentes Ambientais/envenenamento , Humanos , Hipertensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Projetos Piloto , Espectrometria de Massas em Tandem
20.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31653115

RESUMO

Cardiovascular disease (CVD) is common in chronic kidney disease (CKD), while major CV events are rare in young CKD patients. In addition to nitric oxide (NO)-related biomarkers, several surrogate markers have been assessed to stratify CV risk in youth with CKD, including 24-h ambulatory blood pressure monitoring (ABPM), carotid artery intima-media thickness (cIMT), pulse wave velocity (PWV), ABPM-derived arterial stiffness index (AASI), flow-mediated dilatation (FMD), and left ventricular mass index (LVMI). The aim of this study was to identify subclinical CVD through the analysis of indices of CV risk in children and adolescents with CKD. Between 2016 and 2018, the prospective observational study enrolled 125 patients aged 3 to 18 years with G1-G4 CKD stages. Close to two-thirds of young patients with CKD exhibited blood pressure (BP) abnormalities on ABPM. CKD children with abnormal office BP showed lower plasma arginine levels and arginine-to-asymmetric dimethylarginine (ADMA) ratio, but higher ratios of ADMA-to-symmetric dimethylarginine (SDMA) and citrulline-to-arginine. High PWV and AASI, indices of arterial stiffness, both strongly correlated with high BP load. Additionally, LV mass and LVMI exhibited strong correlations with high BP load. Using an adjusted regression model, we observed the citrulline-to-arginine ratio was associated with 24-h systolic and diastolic BP, systolic blood pressure (SBP) load, and diastolic blood pressure (DBP) load. Early assessments of NO-related parameters, BP load abnormalities, arterial stiffness indices, and LV mass will aid in early preventative care toward decreasing CV risk later in life for children and adolescents with CKD.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Óxido Nítrico/metabolismo , Insuficiência Renal Crônica/patologia , Adolescente , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/metabolismo , Doenças Cardiovasculares/etiologia , Criança , Pré-Escolar , Feminino , Ventrículos do Coração/química , Ventrículos do Coração/metabolismo , Humanos , Masculino , Estudos Prospectivos , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Fatores de Risco , Índice de Gravidade de Doença , Rigidez Vascular
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