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1.
Wiad Lek ; 72(9 cz 2): 1781-1785, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622266

RESUMO

OBJECTIVE: Introduction: Polytrauma or multiple organ damage is associated with shock and lead to systemic inflammation, oxidative stress and endothelial dysfunction. A severe mechanical injury causes an increased proinflammatory mediators and cytokines levels. Among them, the overproduction of nitric oxide and its oxidation products play a key role in tissue damage. The aim: To evaluate the changes in dynamics of some ornithine cycle components levels during acute period of polytrauma. PATIENTS AND METHODS: Materials and methods: We measured standard biomechanical parameters and serum levels of NO, sum of nitrite and nitrate (NOx), L-arginine, arginase, and peroxynitrite. According to the ISS, the study included patients with moderate (n=15) to severe (n=15) polytrauma. RESULTS: Results: In 24 hours after polytrauma on the background of intensive care, it was observed significant increasing of NO, NOx, and arginase levels (severe cases) with decreasing of L-arginine and peroxynitrite levels. CONCLUSION: Conclusions: Elevated NO and NOx serum levels in patients with polytrauma is associated with increasing of arginase activity with decreasing of L-arginine and peroxynitrite levels on the background of intensive care.


Assuntos
Traumatismo Múltiplo/diagnóstico , Ornitina/metabolismo , Arginase/sangue , Arginina/sangue , Humanos , Traumatismo Múltiplo/sangue , Nitratos/sangue , Óxido Nítrico/sangue , Nitritos/sangue , Ácido Peroxinitroso/sangue
2.
BMC Complement Altern Med ; 19(1): 127, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196042

RESUMO

BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Angiotensina II , Animais , Aorta/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/sangue , Pressão Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Malondialdeído/sangue , Camundongos , Miocárdio/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Superóxido Dismutase/sangue
3.
Life Sci ; 231: 116577, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31211997

RESUMO

PURPOSE: Galectin-3 is associated with the process of inflammation and fibrosis. The aim of this study was both to evaluate of galectin-3, methylated arginines and hs-CRP in subjects with type 2 diabetes and prediabetes and to investigate a relation between serum galectin-3, methylated arginines and hs-CRP levels. METHODS: In this study, all subjects were defined as the control group, type 2 diabetes (n = 84) by fasting plasma glucose and prediabetes (n = 34) by 75-g oral glucose tolerance test. Also, participants with type 2 diabetes were divided into as group I (HbA1c ≤7%, n = 40) and group II (HbA1c ≥7%, n = 44). The analysis of serum methylated arginines levels was analyzed by tandem mass spectrometry. Galectin-3 levels were determined via chemiluminescent microparticle immunoassay (CMIA). RESULTS: Serum galectin-3, ADMA, L-NMMA and SDMA levels were significantly lower in the control group (13.3 ±â€¯3.42; 0.630 (0.13-1.36); 0.176 (0.02-0.53); 0.115 (0.04-0.26), respectively) compared to diabetic subjects (15.71 ±â€¯4.22; 0.825 (0.23-2.80); 0.366 (0.08-1.41); 0.1645 (0.06-0.47), p = 0.002, p = 0.01, p = 0.001 and p = 0.006, respectively). Galectin-3 was positively correlated with hs-CRP (r = 0.295 p = 0.001), L-NMMA (r = 0.181 p = 0.022), HbA1c (r = 0.247 p = 0.002), neopterin (r = 0.160 p = 0.045) and FPG (r = 0.207 p = 0.001) respectively. Also, there was positively correlated ADMA with FPG (r = 0.192 p = 0.016) and eAG (r = 0.235 p = 0.003). CONCLUSIONS: Thus, galectin-3 might be a useful prognostic marker in the population with prediabetes and diabetes. Moreover, it can be a marker showing the condition of developing complications in diabetic patients.


Assuntos
Arginina/sangue , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Galectina 3/sangue , Estado Pré-Diabético/sangue , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Jejum/sangue , Feminino , Galectina 3/análise , Teste de Tolerância a Glucose , Hemoglobina A Glicada/metabolismo , Humanos , Resistência à Insulina , Masculino , Metilação , Pessoa de Meia-Idade
4.
Chin J Integr Med ; 25(5): 327-333, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065970

RESUMO

OBJECTIVE: To examine the prognostic value of serum levels of asymmetric dimethylarginine (ADMA) in patients with stable coronary heart disease (CHD) thus explore a potential biomarker of "toxin syndrome" in CHD. METHODS: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event (RCE) during 1-year follow-up. Serum levels of ADMA at the start of follow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. RESULTS: Based on the crude model, subjects in the 2 highest ADMA quartiles showed significantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio (OR) 4.09, 95% confidence interval (CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model (OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model (OR 6.64, 95% CI 1.40 to 31.49: OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein (hsCRP) showed better predictive power with areas under the receiver operator characteristic curves (0.779) than the model of either ADMA (0.694) or hsCRP (0.636). CONCLUSION: Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is ChiCTR-PRNRC-07000012].


Assuntos
Arginina/análogos & derivados , Doença das Coronárias/sangue , Arginina/sangue , Biomarcadores/sangue , Humanos , Razão de Chances , Curva ROC , Recidiva , Fatores de Risco , Síndrome
5.
Mol Cell Biochem ; 458(1-2): 133-142, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093850

RESUMO

Changes in the ecto-5'-nucleotidase activity-an extracellular nucleotide catabolic enzyme may lead to the inflammation and endothelial dysfunction. We investigated the effect of CD73 deletion on the endothelial function and L-arginine metabolism in various age groups of mice. 1-,3-,6-, and 12-month-old, male C57BL/6 J wild type (WT) and C57BL/6 J CD73-/- (CD73-/-) mice were used. Blood samples were used for the analysis of adenine nucleotide concentrations. Serum samples were analyzed for the concentration of amino acids, Interleukin 6 (IL-6), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and endothelial nitric oxide synthase (eNOS) level. Serum and aortic nitrate/nitrite, as well as aortic arginase and NOS activity in endothelial cells (EC) were evaluated. CD73 deletion led to age-dependent increase in IL-6, ICAM-1, and VCAM-1 concentration compared to WT. All CD73-/- mice age groups were characterized by reduced L-Arginine concentration and eNOS level. Significantly lower NOS activity was noticed in EC isolated from CD73-/- mice lungs in comparison to EC isolated from WT lungs. The L-Arginine/ADMA ratio in the CD73-/- decreased in age-dependent manner in comparison to WT. The nitrate/nitrite ratio was reduced in serum and in aortas of 6-month-old CD73-/- mice as compared to WT. The ornithine/arginine and ornithine/citrulline ratios were increased in CD73-/- compared to controls. Blood (erythrocyte) Adenosine-5'-triphosphate and Adenosine-5'-diphosphate levels were reduced in favor to higher blood Adenosine-5'-monophosphate concentration in CD73-/- mice in comparison to WT. The CD73 deletion leads to the development of age-dependent endothelial dysfunction in mice, associated with impaired L-arginine metabolism. CD73 activity seems to protect endothelium.


Assuntos
5'-Nucleotidase/deficiência , Arginina/sangue , Endotélio Vascular/metabolismo , Difosfato de Adenosina/sangue , Difosfato de Adenosina/genética , Trifosfato de Adenosina/sangue , Trifosfato de Adenosina/genética , Animais , Arginina/genética , Endotélio Vascular/patologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Interleucina-6/sangue , Interleucina-6/genética , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/sangue , Óxido Nítrico Sintase Tipo III/genética , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética
6.
Amino Acids ; 51(6): 977-982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31049693

RESUMO

High plasma osteoprotegerin (OPG) and asymmetric dimethylarginine (ADMA) and low homoarginine (hArg) predict adverse renal and cardiovascular (CV) outcomes. In patients with chronic kidney disease and stable coronary artery disease, plasma OPG correlated with hArg (r = - 0.37, P = 0.03) and the hArg/ADMA molar ratio (r = - 0.46, P = 0.009), which was maintained upon adjustment for renal function. Elevated OPG levels and decreased hArg/ADMA ratios independently predicted 4-year composite CV and renal endpoints (CV death or progression to dialysis). Thus, high OPG and low hArg/ADMA ratio, albeit interrelated, appear to independently contribute to adverse clinical outcome.


Assuntos
Arginina/análogos & derivados , Doença da Artéria Coronariana/sangue , Homoarginina/sangue , Osteoprotegerina/sangue , Insuficiência Renal Crônica/sangue , Idoso , Arginina/sangue , Biomarcadores/sangue , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologia
7.
Ideggyogy Sz ; 72(3-4): 79-88, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30957461

RESUMO

Background and purpose: Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS). Methods: A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded. Results: Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p<0.001). Both ADMA (p<0.001) and symmetric dimethylarginine (SDMA) (p<0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p<0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 µmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029). Conclusion: Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.


Assuntos
Arginina/sangue , Arginina/metabolismo , Biomarcadores/sangue , Isquemia Encefálica , Acidente Vascular Cerebral/sangue , Fibrilação Atrial , Humanos , Acidente Vascular Cerebral/etiologia
8.
Biomed Res Int ; 2019: 2941861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30931324

RESUMO

Objective: The purpose of the meta-analysis was to evaluate the relationship between serum asymmetric dimethylarginine (ADMA) level and microvascular complications in diabetes mellitus (DM) including diabetic retinopathy (DR), diabetic neuropathy (DN), and diabetic nephropathy. Methods: Studies were comprehensively identified by searching Web of Science, Embase, and PubMed databases up to August 30, 2018. The meta-analysis was carried out to compare the difference of serum ADMA concentrations of DR, DN, and diabetic nephropathy patients with healthy controls. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality were applied to assess the methodological quality. Chi-squared Q test and I2 statistics were applied to evaluate statistical heterogeneity. Subgroup analyses were conducted and publication bias was assessed by Egger's test. Result: Ten studies were finally entered in the meta-analysis. Statistically significant heterogeneity was observed across these studies (I 2 = 77.0%, p < 0.001). Compared with DM without microvascular complications, circulating level of ADMA was significantly higher in DM with microvascular complications (all p < 0.05). Sensitivity analysis suggested that the results of this meta-analysis were shown to be stable. There was no significant publication bias (P=0.823). Conclusion: Elevated ADMA levels correlate with diabetic microangiopathies such as DR and diabetic nephropathy. ADMA may play an important role in the pathobiology of microvascular complications of diabetes.


Assuntos
Arginina/análogos & derivados , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Nefropatias Diabéticas/sangue , Arginina/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/patologia , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/patologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/patologia , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/patologia , Feminino , Humanos , Masculino , Fatores de Risco
9.
Artigo em Inglês | MEDLINE | ID: mdl-30990116

RESUMO

4-pyridone-3-carboxamide-1-ß-D-ribonucleoside (4PYR) is a new nicotinamide derivative, which is potentially toxic to the endothelium. Dysfunction of the endothelium promotes cancer cell proliferation, invasiveness, and inflammatory signaling. The aim of this study was to analyze 4PYR concentration in the plasma of lung cancer patients and its relationship to other known biochemical parameters associated with the endothelium function. The concentration of 4PYR, nicotinamide, 1-methylnicotinamide (MNA), amino acids, and their derivatives were measured in samples obtained from patients with primary squamous cell carcinoma (n = 48) and control group (n = 100). The concentration of 4PYR and 4PYR/MNA ratio were significantly higher in lung cancer patients as compared to controls (0.099 ± 0.009 vs. 0.066 ± 0.006 µmol/L and 1.10 ± 0.08 vs. 1.97 ± 0.15, respectively). The plasma arginine/asymmetric dimethylarginine (Arg/ADMA) ratio was considerably lower in lung cancer patients (253 ± 17 vs. 369 ± 19) as well as plasma MNA (0.057 ± 0.004 vs. 0.069 ± 0.003 µmol/L). There was no difference in the plasma concentrations of nicotinamide and nicotinamide riboside in both groups (0.116 ± 0.019 vs. 0.131 ± 0.014 and 0.102 ± 0.006 vs. 0.113 ± 0.011, respectively). In this study, a higher 4PYR concentration was observed for the first time in patients with squamous cell carcinoma. This change may be related to the endothelial dysfunction that promote cancer progression since 4PYR and its derivatives are known to disrupt glycolytic pathway.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Nucleosídeos/sangue , Piridonas/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Carcinoma de Células Escamosas/patologia , Células Endoteliais/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Niacinamida/sangue , Espectrometria de Massas em Tandem/métodos
10.
Amino Acids ; 51(6): 961-971, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31028565

RESUMO

The importance of L-arginine (Arg) and relatives, including L-homoarginine (hArg) and asymmetric dimethylarginine (ADMA), in humans infected with Helicobacter pylori (Hp) is little understood. ADMA is produced by asymmetric dimethylation of the guanidine group of Arg residues in certain proteins and is released by proteolysis. High concentrations of circulating free ADMA are considered a risk factor for morbidity and mortality in adults. This risk is considered to arise from the inhibition of the synthesis of nitric oxide (NO), which is a potent vasodilator and inhibitor of platelet aggregation. In the present study, we quantified by stable isotope dilution gas chromatography-mass spectrometry (GC-MS) the concentration of free (f) and total (t) ADMA, Arg, hArg, lysine (Lys) and the sum of citrulline (Cit) and ornithine (Orn) (6 M HCl, 20 h, 110 °C) in serum samples of apparently healthy elderly subjects (n = 27; age, 31-105 years) who were tested for Hp infection. Nine subjects (5 males, 4 females) were found to be Hp seropositive (Hp+) and 18 subjects (8 males, 9 females) were found to be Hp seronegative (Hp‒). Proteinic (p) concentrations were determined by difference. fADMA (0.493 ± 0.068 vs 0.466 ± 0.081 µM, P = 0.382), pADMA (113 ± 73 vs 76 ± 59 nM, P = 0.169) and tADMA (0.606 ± 0.126 vs 0.543 ± 0.121 µM, P = 0.280) serum concentrations were found not to differ between the Hp+ and Hp- subjects. Serum concentrations of fArg (162 ± 30 vs 177 ± 36 µM, P = 0.471), fhArg (1.600 ± 0.638 vs 1.831 ± 0.742 µM, P = 0.554), and fLys (388 ± 170 vs 395 ± 149 µM, P = 0.700) also did not differ statistically between Hp+ and Hp- subjects. tArg (12.4 ± 1.49 vs 13.0 ± 1.33 mM, P = 0.190), tLys (23.0 ± 2.65 vs. 23.9 ± 2.66 mM, P = 0.456) and tCit + Orn (2.53 ± 0.76 vs 2.63 ± 0.85 mM, P = 0.817) did not differ between Hp+and Hp‒ subjects as well. phArg concentration was close to the limit of quantitation of the method (Hp+: 30 ± 210 nM; Hp-: 42 ± 205 nM), suggesting that hArg is virtually absent in serum proteins of the investigated subjects. pCit + Orn did not differ between infected and non-infected subjects. Our study suggests that Hp infection is not associated with elevated asymmetric dimethylation and citrullination of Arg proteins present in the serum or with the hArg synthesis from free Arg in elderly subjects. However, asymmetric Arg dimethylation was found to correlate inversely with Arg citrullination in Hp- (r2 = 0.408, P = 0.004) but not in Hp+ (r2 = 0.065, P = 0.506), with Arg citrullination decreasing and Arg asymmetric dimethylation increasing with subjects' age.


Assuntos
Arginina/análogos & derivados , Citrulinação , Citrulina/sangue , Infecções por Helicobacter/sangue , Homoarginina/sangue , Metilação , Adulto , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Arginina/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Infecções por Helicobacter/patologia , Helicobacter pylori/metabolismo , Humanos , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/biossíntese , Ornitina/sangue
11.
J Anim Physiol Anim Nutr (Berl) ; 103(3): 791-800, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30815917

RESUMO

Forty-eight Duroc × Large White × Landrace pigs with an average initial body weight of 77.09 ± 1.37 kg were used to investigate the effects of combination of leucine (Leu) with arginine (Arg) or glutamic acid (Glu) on muscle growth, free amino acid profiles, expression levels of amino acid transporters and growth-related genes in skeletal muscle. The animals were randomly assigned to one of the four treatment groups (12 pigs/group, castrated male:female = 1:1). The pigs in the control group were fed a basal diet (13% Crude Protein), and those in the experimental groups were fed the basal diet supplemented with 1.00% Leu (L group), 1.00% Leu + 1.00% Arg (LA group) or 1.00% Leu + 1.00% Glu (LG group). The experiment lasted for 60 days. Results showed an increase (p < 0.05) in biceps femoris (BF) muscle weight in the L group and LG group relative to the basal diet group. In longissimus dorsi (LD) muscle, Lys, taurine and total essential amino acid concentration increased in the LG group relative to the basal diet group (p < 0.05). In LG group, Glu and carnosine concentrations increased (p < 0.05) in the BF muscle, when compared to the basal diet group. The Leu and Lys concentrations of BF muscle were lower in the LA group than that in the L group (p < 0.05). A positive association was found between BF muscle weight and Leu concentration (p < 0.05). The LG group presented higher (p < 0.05) mRNA levels of ASCT2, LAT1, PAT2, SANT2 and TAT1 in LD muscle than those in the basal diet group. The mRNA levels of PAT2 and MyoD in BF muscle were upregulated (p < 0.05) in the LG group, compared with those in the basal diet group. In conclusion, Leu alone or in combination with Glu is benefit for biceps femoris muscle growth in fattening pig.


Assuntos
Arginina/farmacologia , Ácido Glutâmico/farmacologia , Leucina/farmacologia , Músculo Esquelético/crescimento & desenvolvimento , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/administração & dosagem , Arginina/sangue , Dieta/veterinária , Suplementos Nutricionais , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/sangue , Leucina/administração & dosagem , Leucina/sangue , Distribuição Aleatória , Regulação para Cima
12.
J Pharm Biomed Anal ; 169: 82-89, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30844626

RESUMO

Pediatric chronic kidney disease (CKD) is currently assessed using glomerular filtration rate (GFR), which is calculated from different equations based on serum creatinine concentration. However, serum creatinine is affected by several factors and is not reliable enough for the diagnosis of CKD, especially at early stages. Recent targeted and untargeted metabolomics studies found 7 new potential biomarkers that could be useful for early pediatric chronic kidney disease diagnosis. Thus, a new LC-QQQ-MS analytical method has been developed and validated aimed at routine analysis of these 7 potential biomarkers: NG,NG'-dimethyl-l-arginine di(p-hydroxyazobenzene-p'-sulfonate) (SDMA), S-adenosyl-l-methionine (SAM), n-butyryl-l-carnitine (nC4), iso-butyryl-l-carnitine (iC4), citrulline (CIT), creatinine (CNN) and d-erytro-sphingosine-1-phosphate (S1P), in addition to creatinine, the classical biomarker for CKD diagnosis. Then, this analytical method has been used for the quantification of plasma samples from a heterogeneous group of CKD pediatric patients and a control pediatric population. Data analysis of these results showed that it is possible to differentiate between CKD and control populations based on the metabolite concentration in plasma.


Assuntos
Biomarcadores/sangue , Biomarcadores/química , Plasma/química , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Arginina/análogos & derivados , Arginina/sangue , Arginina/química , Criança , Pré-Escolar , Cromatografia Líquida/métodos , Citrulina/química , Creatinina/sangue , Diagnóstico Precoce , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Metabolômica/métodos , S-Adenosilmetionina/sangue , S-Adenosilmetionina/química , Espectrometria de Massas em Tandem/métodos
13.
Amino Acids ; 51(5): 773-782, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30830311

RESUMO

Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the Q statistic and quantified using I2. Publication bias was evaluated using a funnel plot and Egger's linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.


Assuntos
Arginina/análogos & derivados , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Arginina/sangue , Estudos de Casos e Controles , Humanos , Fatores de Risco
14.
Amino Acids ; 51(6): 913-927, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915571

RESUMO

Cardiovascular disease (CVD) is the leading cause of death in renal transplant recipients (RTR). Elevated plasma asymmetric dimethylarginine (pADMA), an endogenous nitric oxide synthase inhibitor produced from the turnover of methylated arginine moieties in proteins, is a risk factor for CVD and mortality. It is unknown how urinary ADMA excretion (uADMA), one of the main ADMA elimination routes, is associated with long-term survival. Furthermore, the association of pADMA and uADMA with markers for turnover of arginine-methylated proteins is unknown. We analyzed ADMA using a validated GC-MS/MS method in plasma and 24-h urine samples of 685 RTR, included ≥ 1 year after transplantation. We also analyzed urine symmetric dimethylarginine (uSDMA) using the same method. Urinary creatinine and urea excretions were used as markers for turnover of muscle protein and amino acids, respectively. We applied Cox regression analyses to study associations of pADMA, uADMA, and uSDMA with all-cause and CVD mortality. Mean pADMA was 0.61 ± 0.12 µM, uADMA was 31 ± 13 µmol/24 h, and uSDMA was 52 ± 19 µmol/24 h. Over median follow-up of 5.4 [4.9-6.1] years, 147 RTR died, of which 58 (39%) from CVD. High pADMA was associated with high all-cause mortality (HR per SD [95% CI]: 1.45 [1.26-1.67], P < 0.001), while high uADMA was associated with low all-cause and CVD mortality (HR per SD [95% CI]: 0.57 [0.47-0.69], P < 0.001, and 0.55 [0.40-0.74], P < 0.001, respectively). The associations were independent of adjustment for potential confounders. Creatinine excretion was associated with both pADMA (st. ß:- 0.21, P = 0.003) and uADMA (st. ß: 0.49, P < 0.001), and urea excretion was associated with uADMA (st. ß: 0.56, P < 0.001). Associations of uSDMA with outcomes and with creatinine excretion and urea excretion were comparable to those of uADMA. The associations of pADMA, uADMA and uSDMA with mortality were strongly affected by adjustment for creatinine excretion and urea excretion. We found for the first time that high uADMA and high uSDMA are associated with less risk of all-cause and CVD mortality. The links of uADMA and uSDMA with markers of muscle protein and amino acid turnover may serve to further understand ADMA and SDMA homeostasis and their clinical implications.


Assuntos
Arginina/análogos & derivados , Doenças Cardiovasculares , Transplante de Rim/efeitos adversos , Adulto , Arginina/sangue , Arginina/urina , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/urina , Creatinina/urina , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Espectrometria de Massas em Tandem , Transplantados
15.
Mol Genet Metab ; 126(4): 397-405, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30827756

RESUMO

BACKGROUND AND AIM: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients. METHODS: We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels. CONCLUSION: Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Aminoácidos de Cadeia Ramificada/sangue , Arginina/sangue , Transtornos do Crescimento/etiologia , Acidemia Propiônica/complicações , Distúrbios Congênitos do Ciclo da Ureia/complicações , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Estatura , Criança , Pré-Escolar , Dieta , Europa (Continente) , Feminino , Transtornos do Crescimento/dietoterapia , Humanos , Estudos Longitudinais , Masculino , Sistema de Registros
16.
Pediatr Emerg Care ; 35(3): 226-230, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30747788

RESUMO

OBJECTIVE: Carbon monoxide poisoning (COP) is the leading cause of mortality and morbidity due to poisoning worldwide. Because children are affected more quick and severely from COP, they may require a longer treatment period, even if carboxyhemoglobin (CO-Hb) and/or lactate levels return to normal. Therefore, a new marker that predicts the duration of treatment and the final outcomes of COP is needed. METHODS: This case control study was conducted on 32 carbon monoxide-poisoned patients younger than 18 years who had been admitted to pediatric emergency department. The control group included age- and sex-matched 30 healthy children. Blood samples were obtained for analysis of arterial blood gases, CO-Hb percent, methemoglobine, lactate, and asymmetric dimethylarginine (ADMA). RESULTS: Asymmetric dimethylarginine levels were significantly increased (P < 0.05) in patients with COP on admission and after the treatment when compared with controls (1.36 [0.89-6.94], 1.69 [0.76-7.81], 1.21 [0.73-3.18] nmol/L, respectively). There was no positive correlation between CO-Hb and ADMA levels on admission and at 6 hours (P = 0.903, r = 0.218, P = 0.231, r = 0.022, respectively). Positive correlation was found between lactate and CO-Hb levels on admission (P = 0.018, r = 0.423). CONCLUSIONS: This study showed that ADMA levels were still high after 6 hours of 100% oxygen therapy in children with COP, even CO-Hb and/or lactate levels return to normal range. On the basis of these results, we consider that ADMA may be a useful biomarker in patient with COP.


Assuntos
Arginina/análogos & derivados , Biomarcadores/sangue , Intoxicação por Monóxido de Carbono/sangue , Adolescente , Arginina/sangue , Gasometria/métodos , Intoxicação por Monóxido de Carbono/terapia , Carboxihemoglobina/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Metemoglobina/análise
17.
Clin Chim Acta ; 492: 29-36, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30731087

RESUMO

BACKGROUND: Changes in NO metabolism correlate with cardiovascular risk factors and are associated with endothelial dysfunction. NO availability is regulated by nitric oxide synthase (NOS) and arginine and some chemically related metabolites and analogs have the capacity to alter NOS activity. Hence the need for analytical methods for the simultaneous assessment of these analytes. METHODS: Analytes (L-arginine (Arg), NG-monomethyl-L-arginine (MMA), L-homoarginine (hArg), asymmetric dimethyl-L-arginine (ADMA), symmetric dimethyl-L-arginine (SDMA), and L-citrulline (CIT)) were isolated from human plasma by thermal coagulation of plasma followed by a derivatization with diethylpyrocarbonate. Carbetoxy derivatives were separated on a C18 reversed-phase column in <10 min using an aqueous solution of 0.4% v/v formic acid and acetonitrile (95:5, v/v) mixture as a mobile phase. Positive electrospray ionization and tandem mass spectrometry in combination with specific multiple reaction monitoring transitions were used for detection of analytes and three deuterated forms of the analytes used as internal standards. RESULTS: Intra- and inter-day precision %RSD values ranged between 3 and 5.5% and percentage recoveries were close to 100% for all analytes. Plasma concentrations in 20 healthy male volunteers were 58.62 ±â€¯8.81 µmol/L for Arg, 105.08 ±â€¯21.66 nmol/L for MMA, 1.88 ±â€¯0.57 µmol/L for hArg, 0.612 ±â€¯0.140 µmol/L for ADMA, 0.581 ±â€¯0.172 µmol/L for SDMA, and 28.62 ±â€¯11.60 µmol/L for Cit, respectively. CONCLUSION: This LC-MS/MS method provides the capacity to quantify the plasma concentrations of arginine and some of its chemically related metabolites. Sample preparation was simple, inexpensive and effortless. Overall, given the short sample preparation and chromatographic run time, the method may be suitable for the fast and reproducible quantitative determination of the analytes in large clinical trials and routine analysis.


Assuntos
Arginina/sangue , Arginina/química , Análise Química do Sangue/métodos , Cromatografia Líquida/métodos , Dietil Pirocarbonato/química , Espectrometria de Massas em Tandem/métodos , Arginina/metabolismo , Humanos , Reprodutibilidade dos Testes , Fatores de Tempo
18.
J Vet Intern Med ; 33(2): 987-998, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30788867

RESUMO

BACKGROUND: Plasma citrulline (CIT) concentration is considered to be a reliable marker of functional enterocyte mass, primarily in humans. However, information about CIT levels along with related metabolites, arginine (ARG), nitric oxide (NO), and ammonia in neonatal calves are lacking. OBJECTIVES: To compare plasma CIT, ARG, NO, and whole blood ammonia concentrations in neonatal calves with acute diarrhea with those in healthy calves and to assess their possible relationships with diarrhea-related criteria. ANIMALS: Seventy neonatal calves (60 with acute diarrhea and 10 healthy). METHODS: Observational case-control study. Diarrheic calves were classified into subgroups on the basis of etiology, severity of diarrhea, degree of dehydration, and systemic inflammatory response syndrome (SIRS) status. Plasma CIT and ARG concentrations were measured by liquid chromatography/tandem mass spectrometry. RESULTS: Plasma CIT (median [range]: 67.5 [61.9-75.4] vs 30.1 [15.0-56.1] µmol/L) and ARG (170.7 [148.5-219.5] vs 106.1 [54.4-190.7] µmol/L) were lower and plasma NO (4.42 [3.29-5.58] vs 6.78 [5.29-8.92] µM) and blood ammonia concentrations (28.7 [26.1-36.9] vs 59.8 [34.6-99.5] µmol/L) were higher in the neonatal calves with diarrhea (P < .001). Plasma CIT (ß = -0.29, P = .02), ARG (ß = -0.33, P = .01), NO (ß = 0.55, P < .001), and blood ammonia (ß = 0.63, P <.001) were affected by SIRS status. Except for ammonia (0.52), the effects sizes for severity of diarrhea and degree of dehydration were small (ηp2 ≤ 0.45) for CIT, ARG, and NO. CONCLUSIONS AND CLINICAL IMPORTANCE: The changes in these variables might have diagnostic, prognostic, and therapeutic value in diarrheic neonatal calves.


Assuntos
Amônia/sangue , Arginina/sangue , Doenças dos Bovinos/sangue , Citrulina/sangue , Diarreia/veterinária , Óxido Nítrico/sangue , Animais , Animais Recém-Nascidos/sangue , Estudos de Casos e Controles , Bovinos , Desidratação/veterinária , Diarreia/sangue , Síndrome de Resposta Inflamatória Sistêmica/veterinária
19.
Int J Mol Sci ; 20(3)2019 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-30744089

RESUMO

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA2DS2VASC score, and the carotid intima⁻media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA2DS2VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.


Assuntos
Arginina/análogos & derivados , Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Espessura Intima-Media Carotídea , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Biomarcadores , Endotélio/metabolismo , Endotélio/patologia , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia
20.
J Vet Intern Med ; 33(2): 508-515, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30758070

RESUMO

BACKGROUND: Iatrogenic hypothyroidism might worsen the prognosis of cats with azotemic CKD after thyroidectomy. Varying thyroxine concentrations influence utility of creatinine in assessing renal function. Symmetric dimethylarginine (SDMA) has limited studies in cats with changing thyroid status. OBJECTIVES: Thyroid status is stable 6 months post-thyroidectomy. Symmetric dimethylarginine and creatinine are linearly associated without influence from total thyroxine concentration (tT4). ANIMALS: Electronic records of 2 first opinion practices were searched using the term "thyroidectomy" to include 81 client-owned cats that had undergone bilateral thyroidectomy. METHODS: Retrospective cross-sectional study assessing thyroid hormone concentrations of 68 cats within 6 months of surgery. A longitudinal study of thyroid status in 23 cats with >18 months follow-up post-thyroidectomy. A generalized estimating equation assessed the associations of bodyweight, tT4 and creatinine concentrations on SDMA concentration. RESULTS: Sixty-eight cats had follow-up within 6 months. Fifteen cats (22%) had persistent, or recurrent, hyperthyroidism and 33 cats (49%) were hypothyroid. Twenty-three of the euthyroid/hypothyroid cats had long-term follow-up (595-1955 days); 4 cats (17%) remained hypothyroid, 19 cats (83%) were euthyroid (often transiently), and 9 of 23 cats (44%) developed recurrent hyperthyroidism. Symmetric dimethylarginine and creatinine were linearly associated, but hyperthyroid cats had higher SDMA concentrations, relative to creatinine (P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats have changes in thyroid function for years after bilateral thyroidectomy, with a high incidence of recurrent hyperthyroidism. Both SDMA and creatinine are affected by thyroxine concentrations, and the effect is greater in hyperthyroid cats.


Assuntos
Arginina/análogos & derivados , Azotemia/veterinária , Doenças do Gato/etiologia , Tireoidectomia/veterinária , Animais , Arginina/sangue , Azotemia/sangue , Peso Corporal , Doenças do Gato/sangue , Doenças do Gato/patologia , Gatos , Creatinina/sangue , Estudos Transversais , Hipertireoidismo/complicações , Hipertireoidismo/veterinária , Hipotireoidismo/complicações , Hipotireoidismo/veterinária , Estudos Longitudinais , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Tiroxina/sangue
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