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1.
Front Immunol ; 12: 695972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34341659

RESUMO

COVID-19 ranges from asymptomatic in 35% of cases to severe in 20% of patients. Differences in the type and degree of inflammation appear to determine the severity of the disease. Recent reports show an increase in circulating monocytic-myeloid-derived suppressor cells (M-MDSC) in severe COVID 19 that deplete arginine but are not associated with respiratory complications. Our data shows that differences in the type, function and transcriptome of granulocytic-MDSC (G-MDSC) may in part explain the severity COVID-19, in particular the association with pulmonary complications. Large infiltrates by Arginase 1+ G-MDSC (Arg+G-MDSC), expressing NOX-1 and NOX-2 (important for production of reactive oxygen species) were found in the lungs of patients who died from COVID-19 complications. Increased circulating Arg+G-MDSC depleted arginine, which impaired T cell receptor and endothelial cell function. Transcriptomic signatures of G-MDSC from patients with different stages of COVID-19, revealed that asymptomatic patients had increased expression of pathways and genes associated with type I interferon (IFN), while patients with severe COVID-19 had increased expression of genes associated with arginase production, and granulocyte degranulation and function. These results suggest that asymptomatic patients develop a protective type I IFN response, while patients with severe COVID-19 have an increased inflammatory response that depletes arginine, impairs T cell and endothelial cell function, and causes extensive pulmonary damage. Therefore, inhibition of arginase-1 and/or replenishment of arginine may be important in preventing/treating severe COVID-19.


Assuntos
COVID-19/imunologia , Granulócitos/imunologia , Células Supressoras Mieloides/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Arginase/antagonistas & inibidores , Arginase/metabolismo , Arginina/administração & dosagem , Arginina/sangue , Arginina/metabolismo , Infecções Assintomáticas , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Estudos de Casos e Controles , Quimioterapia Combinada/métodos , Inibidores Enzimáticos/administração & dosagem , Feminino , Granulócitos/metabolismo , Voluntários Saudáveis , Humanos , Interferon Tipo I/metabolismo , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/imunologia , Linfócitos T/imunologia
2.
Nutrients ; 13(7)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34371816

RESUMO

(1) Background: Type-2-diabetes-mellitus (DM) is one the most important cardiovascular-risk-factors. Among many molecules regulating vascular tone, nitric oxide appears to be the most pivotal. Although micro- and macrovascular-abnormalities are extensively studied, the alterations in the nitric-oxide-metabolic-pathway require further investigations. Additionally, the role of erythrocytes in the vascular tone regulation has not been extensively explored. The aim of this study was to evaluate the endothelial-function and the nitric-oxide-metabolic-pathway in erythrocytes and plasma of diabetic individuals. (2) Methods: A total of 80 subjects were enrolled in this cross-sectional study, including 35 patients with DM and 45 healthy individuals. The endothelial-function was evaluated in response to different stimuli. (3) Results: In the DM group, decreased Arginine and citrulline concentrations in the plasma compartment with reduced Arginine/ADMA and ADMA/DMA-ratios were observed. Preserved nitric-oxide-metabolism in erythrocytes with reduced citrulline level and significantly higher NO-bioavailability were noted. Significant endothelial dysfunction in DM individuals was proved in response to the heat-stimulus. (4) Conclusions: DM patients at an early stage of disease show significant differences in the nitric-oxide-metabolic-pathway, which are more pronounced in the plasma compartment. Erythrocytes constitute a buffer with a higher nitric-oxide-bioavailability, less affected by the DM-related deviations. Patients at an early-stage of DM reveal endothelial-dysfunction, which could be diagnosed earlier using the laser-Doppler-flowmetry.


Assuntos
Arginina/análogos & derivados , Arginina/sangue , Diabetes Mellitus Tipo 2/sangue , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Óxido Nítrico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Citrulina/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade
3.
Biomolecules ; 11(7)2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34356664

RESUMO

Aging causes oxidative stress, endothelial dysfunction and a reduction in the bioavailability of nitric oxide. The study aim was to determine whether, as a result of repeated whole-body exposure to cryogenic temperature (3 min -130 °C), there is an increase of inducible nitric oxide synthase (iNOS) concentration in senior subjects (59 ± 6 years), and if this effect is stronger in athletes. In 10 long-distance runners (RUN) and 10 untraining (UTR) men, 24 whole-body cryotherapy (WBC) procedures were performed. Prior to WBC, after 12th and 24th treatments and 7 days later, the concentration of iNOS, asymmetric dimethylarginine (ADMA), 3-nitrotyrosine (3-NTR), homocysteine (HCY), C-reactive protein (CRP) and interleukins such as: IL-6, IL-1ß, IL-10 were measured. In the RUN and UTR groups, after 24 WBC, iNOS concentration was found to be comparable and significantly higher (F = 5.95, p < 0.01) (large clinical effect size) compared to before 1st WBC and after 12th WBC sessions. There were no changes in the concentration of the remaining markers as a result of WBC (p > 0.05). As a result of applying 24 WBC treatments, using the every-other-day model, iNOS concentration increased in the group of older men, regardless of their physical activity level. Along with this increase, there were no changes in nitro-oxidative stress or inflammation marker levels.


Assuntos
Crioterapia/métodos , Óxido Nítrico Sintase Tipo II/sangue , Idoso , Arginina/análogos & derivados , Arginina/sangue , Atletas , Índice de Massa Corporal , Exercício Físico , Humanos , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Resistência Física , Tirosina/análogos & derivados , Tirosina/sangue
4.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R364-R376, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259017

RESUMO

Preeclampsia is a spontaneously occurring pregnancy complication diagnosed by new-onset hypertension and end-organ dysfunction with or without proteinuria. This pregnancy-specific syndrome contributes to maternal morbidity and mortality and can have detrimental effects on fetal outcomes. Preeclampsia is also linked to increased risk of maternal cardiovascular disease throughout life. Despite intense investigation of this disorder, few treatment options are available. The aim of this study was to investigate the potential therapeutic effects of maternal l-citrulline supplementation on pregnancy-specific vascular dysfunction in the male C57BL/6J × female C57BL/6J C1q-/- preeclampsia-like mouse model. l-Citrulline is a nonessential amino acid that is converted to l-arginine to promote smooth muscle and blood vessel relaxation and improve nitric oxide (NO)-mediated vascular function. To model a preeclampsia-like pregnancy, female C57BL/6J mice were mated to C1q-/- male mice, and a subset of dams was supplemented with l-citrulline throughout pregnancy. Blood pressure, systemic vascular glycocalyx, and ex vivo vascular function were investigated in late pregnancy, and postpartum at 6 and 10 mo of age. Main findings show that l-citrulline reduced blood pressure, increased vascular glycocalyx volume, and rescued ex-vivo vascular function at gestation day 17.5 in this preeclampsia-like model. The vascular benefit of l-citrulline also extended postpartum, with improved vascular function and glycocalyx measures at 6 and 10 mo of age. l-Citrulline-mediated vascular improvements appear, in part, attributable to NO pathway signaling. Taken together, l-citrulline supplementation during pregnancy appears to have beneficial effects on maternal vascular health, which may have translational implications for improved maternal cardiovascular health.


Assuntos
Citrulina/farmacologia , Fenômenos Fisiológicos da Nutrição Materna/efeitos dos fármacos , Parto/efeitos dos fármacos , Pré-Eclâmpsia/tratamento farmacológico , Animais , Arginina/sangue , Pressão Sanguínea/efeitos dos fármacos , Citrulina/sangue , Feminino , Camundongos Endogâmicos C57BL , Placenta/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez
5.
J Zoo Wildl Med ; 52(2): 628-637, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130406

RESUMO

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in captive tigers (Panthera tigris). Blood creatinine (Cr) and blood urea nitrogen measurements are inexpensive and common biomarkers used to evaluate renal function. However, several limitations have been reported regarding their sensitivity and interindividual variability. Symmetric dimethylarginine (SDMA) has been suggested to be a more sensitive biomarker that is less affected by extrarenal factors and has a strong correlation with glomerular filtration rate and blood Cr in several species. This project aimed to identify the usefulness of SDMA as an endogenous marker of kidney function in captive tigers. The hypothesis of this study is that increased circulating SDMA is positively associated with increased blood Cr. SDMA and Cr were measured in 65 banked samples (serum and plasma) from 30 individual captive tigers. The samples were collected over a 38-y period and stored at -21°C. SDMA and Cr concentrations were determined using the commercially available SDMA test and enzymatic colorimetric methods, respectively. SDMA had a significant positive association with Cr (for every 1 unit increase of log SDMA, Cr increased by 82%, P = 0.0002). Age and subspecies influenced Cr but not SDMA concentrations. In one animal, blood SDMA increased above the ZIMS reported range. approximately 3.6 mo before Cr increased. SDMA is currently indicated for the diagnosis of CKD in domestic felids and seems also promising in nondomestic felids. Further prospective studies might improve the understanding of the performance of this biomarker.


Assuntos
Arginina/análogos & derivados , Creatinina/sangue , Rim/fisiologia , Insuficiência Renal Crônica/veterinária , Tigres/sangue , Animais , Arginina/sangue , Biomarcadores/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos
6.
Toxicol Lett ; 349: 92-100, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153407

RESUMO

Hexavalent chromium (Cr(VI)) compound is considered as a common environmental and occupational pollutant due to widespread application in industry and agriculture. Cr(VI) as a carcinogen poses a serious threat to human health and the underlying mechanisms need further investigation. Previous studies had demonstrated the characteristic expression profiling after Cr(VI) treatment in vitro and in vivo at the levels of gene and protein. The comprehensive metabolic signatures were also conducive to discover potential biomarkers for effects assessment of Cr(VI) toxicity. In the current study, Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) non-targeted metabolomics was applied to analyze serum metabolic changes in 77 chromate exposure workers and 62 controls. Thirteen metabolites were found significantly decreased and 41 metabolites were increased, which were involved in arginine and proline metabolism, and glycerophospholipid metabolism by bioinformatic analysis. Furthermore, there were significant negative correlations between blood Cr level and Arginine, PC(18:2/24:4) and PC(14:0/16:0), subgroup analyses indicated that these correlations were observed in male-only subgroups, and were not found among chromate workers and controls separately. Diet could be a potential confounder which was not controlled rigorously in this study. These findings provided preliminary clues to investigate the underlying mechanisms of Cr(VI)-induced toxicity and were required to be further verified in future researches.


Assuntos
Cromo/efeitos adversos , Metaboloma/efeitos dos fármacos , Metabolômica , Exposição Ocupacional/efeitos adversos , Proteoma/efeitos dos fármacos , Proteômica , Adulto , Arginina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida , Biologia Computacional , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Saúde do Trabalhador , Fosfatidilcolinas/sangue , Espectrometria de Massas por Ionização por Electrospray
7.
Biomed Pharmacother ; 140: 111773, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34062418

RESUMO

AIMS/INTRODUCTION: The authors evaluated the impact of different dose of metformin on NO (nitric oxide) production in subjects with pre-diabetes. MATERIALS AND METHODS: The metformin-naïve patients from one Diabetic Center with newly diagnosed pre-diabetes, without cardio-vascular diseases, were randomized (based on the identification number, individual for each inhabitant in the country) for treatment with different doses of metformin (group A 3 × 500 mg, group B 3 × 1000 mg) for 12 weeks. Then, the subjects from group B were switched to dose 3 × 500 for the last 3 weeks. The wide panel of L-arginine/NO pathway metabolites concentrations was assessed using the liquid chromatography-mass spectrometry technique. RESULTS: Between October 2017 and December 2018, 36 individuals were initially randomized to intervention groups. The study was completed with 25 subjects: 14 patients in group A, 11 in group B; also 11 healthy volunteers were recruited. There was no difference between participants with pre-diabetes and healthy volunteers as regards the baseline characteristics except for fasting glucose and fatty liver. The decrease of L-citrulline concentration only was reported for treatment groups during the intervention period, with no change for the other NO-production related substances. CONCLUSION: It was the first study on the in vivo release of NO in humans with different metformin doses in patients with pre-diabetes. Metformin did not seem to increase NO production measured by the citrulline plasma levels, irrespective of the dose. The citrulline concentration change might indicate the drug impact on the condition of the enterocytes.


Assuntos
Hipoglicemiantes/farmacologia , Metformina/farmacologia , Óxido Nítrico/biossíntese , Estado Pré-Diabético/sangue , Adulto , Arginina/sangue , Citrulina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Sci Rep ; 11(1): 9895, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972591

RESUMO

COVID-19 is a disease with a variable clinical course ranging from mild symptoms to critical illness, organ failure, and death. Prospective biomarkers may help to predict the severity of an individual's clinical course and mortality risk. We analyzed asymmetric (ADMA) and symmetric dimethylarginine (SDMA) in blood samples from 31 patients hospitalized for COVID-19. We calculated associations of ADMA and SDMA with mortality and organ failure, and we developed a predictive algorithm based upon these biomarkers to predict mortality risk. Nine patients (29%) experienced in-hospital death. SDMA and ADMA serum concentrations were significantly higher at admission in COVID-19 patients who died than in survivors. Cut-offs of 0.90 µmol/L for SDMA (AUC, 0.904, p = 0.0005) and 0.66 µmol/L for ADMA (AUC, 0.874, p = 0.0013) were found in ROC analyses to best discriminate both subgroups of patients. Hazard ratio for in-hospital mortality was 12.2 (95% CI: 2.2-31.2) for SDMA and 6.3 (1.1-14.7) for ADMA above cut-off. Sequential analysis of both biomarkers allowed discriminating a high-risk group (87.5% mortality) from an intermediate-risk group (25% mortality) and a low-risk group (0% mortality). Elevated circulating concentrations of SDMA and ADMA may help to better identify COVID-19 patients with a high risk of in-hospital mortality.


Assuntos
Arginina/análogos & derivados , COVID-19/sangue , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Biomarcadores/sangue , COVID-19/mortalidade , COVID-19/virologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fatores de Risco , SARS-CoV-2/fisiologia
9.
BMC Vet Res ; 17(1): 154, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845861

RESUMO

BACKGROUND: Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs. RESULTS: Thirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 µmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P <  0.0001, P <  0.0001, P = 0.01), 24 h (P <  0.001, P <  0.001, P = 0.002) and 36 h (P <  0.001, P <  0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls. CONCLUSION: Urinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.


Assuntos
Injúria Renal Aguda/veterinária , Biomarcadores/urina , Mordeduras de Serpentes/veterinária , Viperidae , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Animais , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Creatinina/sangue , Doenças do Cão/sangue , Doenças do Cão/urina , Cães , Feminino , Masculino , Mordeduras de Serpentes/sangue , Mordeduras de Serpentes/urina
10.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804011

RESUMO

Asymmetric and symmetric dimethylarginines are toxic non-coded amino acids. They are formed by post-translational modifications and play multifunctional roles in some human diseases. Their determination in human blood plasma is performed using capillary electrophoresis with contactless conductivity detection. The separations are performed in a capillary covered with covalently bonded PAMAPTAC polymer, which generates anionic electroosmotic flow and the separation takes place in the counter-current regime. The background electrolyte is a 750 mM aqueous solution of acetic acid with pH 2.45. The plasma samples for analysis are treated by the addition of acetonitrile and injected into the capillary in a large volume, reaching 94.5% of the total volume of the capillary, and subsequently subjected to electrophoretic stacking. The attained LODs are 16 nm for ADMA and 22 nM for SDMA. The electrophoretic resolution of both isomers has a value of 5.3. The developed method is sufficiently sensitive for the determination of plasmatic levels of ADMA and SDMA. The determination does not require derivatization and the individual steps in the electrophoretic stacking are fully automated. The determined plasmatic levels for healthy individuals vary in the range 0.36-0.62 µM for ADMA and 0.32-0.70 µM for SDMA.


Assuntos
Arginina/análogos & derivados , Eletroforese Capilar , Acetonitrilas/química , Ânions/sangue , Ânions/química , Ânions/isolamento & purificação , Arginina/sangue , Arginina/química , Arginina/isolamento & purificação , Condutividade Elétrica , Humanos , Limite de Detecção
11.
Nutrients ; 13(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805883

RESUMO

The aim of the study was to determine the effect of simultaneous supplementation of ß-hydroxy-ß-methylbutyrate and L-Arginine α-ketoglutarate on lower limb power and muscle damage in medium distance runners aged 15.3 (±0.9) years old. METHODS: The study group consisted of 40 volunteers aged 14-17 years practicing medium distance running for at least two years. The study lasted 12 days and followed a randomized, double-blind, placebo-controlled, parallel design. All subjects attended a familiarization session on day 0 before the test. The subjects were randomly divided into two groups: supplements and placebo group. The same training cycle protocol was used in both groups during the 12-day training period. Morning warm-up involved 10 min jogging at 60-75% of maximal heart rate and countermovement jump height measurement. Main training units were carried out for both groups with the same volume. Training load assessment (the daily session Rating of Perceived Exertion (s-RPE) method) method takes into consideration the intensity and the duration of the training session to calculate the "training load" (TL). RESULTS: At the end of the training cycle, a significant (p = 0.002) decrease in the countermovement jump (CMJ) height was found in the placebo group when compared to the baseline. In the supplement group, there was no decrease in the countermovement jump height. Creatine kinase and lactate dehydrogenase concentration increased during the training days similarly in both groups and decreased on rest days. There were no differences between groups in enzymes concentration. The research results indicate that the supplement combination used in the supplements group prevented a reduction in the CMJ values. In contrast to the supplements group, in the placebo group, the CMJ changes were statistically significant: a noticeable (p = 0.002) decrease in CMJ was noted between the baseline measurement and the 6th measurement. The well-being of the subjects from both groups changed significantly during the training period, and the intergroup differences in the mood level were similar and not statistically significant. CONCLUSIONS: The results of this study indicate that the daily co-supplementation with calcium salt of ß-hydroxy-ß-methylbutyrate (7.5 g) and L-Arginine α-ketoglutarate (10 g) during training might help to prevent decline in jump performance. No influence on muscle damage markers or mood was shown.


Assuntos
Arginina/análogos & derivados , Atletas/estatística & dados numéricos , Desempenho Atlético/estatística & dados numéricos , Ácidos Cetoglutáricos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atletismo , Valeratos/farmacologia , Adolescente , Arginina/sangue , Arginina/farmacologia , Creatina Quinase/sangue , Creatina Quinase/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Ácidos Cetoglutáricos/sangue , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/efeitos dos fármacos , Perna (Membro)/fisiologia , Masculino , Força Muscular/efeitos dos fármacos , Valeratos/sangue
12.
PLoS One ; 16(4): e0249728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33798236

RESUMO

AIM: Osteoporotic fractures negatively impact health-related quality of life and prognosis. Advanced glycation end products (AGEs) impair bone quality and reduce bone strength. The aim of this study was to determine the relationship between plasma levels of pentosidine, a surrogate marker for AGEs, and prevalent fractures in patients with chronic liver disease (CLD). METHODS: This cross-sectional study included 324 patients with CLD. Vertebral fractures were evaluated using lateral thoracolumbar spine radiographs. Information on prevalent fractures was obtained through a medical interview, medical records, and/or radiography. The patients were classified into low (L), intermediate (I), and high (H) pentosidine (Pen) groups based on baseline plasma pentosidine levels. RESULTS: Of the 324 patients, 105 (32.4%) had prevalent fractures. The prevalence of liver cirrhosis (LC) and prevalent fractures significantly increased stepwise with elevated pentosidine levels. The H-Pen group had the highest prevalence of LC (88.6%, p < 0.001) and prevalent fractures (44.3%, p = 0.007), whereas the L-Pen group had the lowest prevalence of LC (32.1%, p < 0.001) and prevalent fractures (21.0%, p = 0.007). Multiple logistic regression analysis identified pentosidine as a significant independent factor related to prevalent fractures (odds ratio = 1.069, p < 0.001). Pentosidine levels increased stepwise and correlated with liver disease severity. They were markedly high in patients with decompensated LC. In multiple regression analysis, liver functional reserve factors (total bilirubin, albumin, and prothrombin time-international normalized ratio) significantly and independently correlated with pentosidine levels. CONCLUSIONS: Plasma pentosidine was significantly associated with prevalent fractures and liver functional reserve in patients with CLD. Pentosidine may be useful in predicting fracture risk and should be closely followed in CLD patients with advanced disease.


Assuntos
Arginina/análogos & derivados , Fraturas Ósseas/sangue , Hepatopatias/sangue , Lisina/análogos & derivados , Idoso , Arginina/sangue , Biomarcadores/sangue , Doença Crônica , Estudos Transversais , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Humanos , Japão/epidemiologia , Hepatopatias/epidemiologia , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Prevalência
13.
Invest Ophthalmol Vis Sci ; 62(4): 7, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33821880

RESUMO

Purpose: Asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of nitric oxide synthase, may be involved in the pathophysiology of glaucoma by dysfunctioning nitric oxide and oxidative stress. The purpose of this study was to determine whether the serum ADMA level is associated with the severity of glaucoma. Methods: One hundred twenty-five patients with glaucoma (mean age 69.4 years) were analyzed in this cross-sectional study. The severity of glaucoma was determined by the visual field mean deviation in the worse eye; severe, a mean deviation ≤ -12 dB; and mild, a mean deviation > -12 dB. The serum ADMA levels were classified into three groups according to tertiles; low (T1), intermediate (T2), and high group (T3). Results: The mean serum ADMA levels in the severe glaucoma group was significantly higher than that in the mild glaucoma group (0.41 vs. 0.39 µmol/L; P = 0.031). A significantly higher prevalence of patients with severe glaucoma was found in the T3 group than that in the T1 group (T1, 44.7% and T3, 68.2%; P = 0.018). In the multivariable logistic regression analysis adjusted for the potential confounders, e.g., age, sex, obesity, smoking, hypertension, diabetes, and renal function, the odds ratio for severe glaucoma in the T3 group was significantly higher than that in the T1 group (odds ratio 3.02; 95% confidence interval 1.04 to 8.79; P = 0.043). Conclusions: A significant association between higher serum ADMA levels and severe glaucoma was found, and this association remained significant after adjusting for the potential confounders.


Assuntos
Arginina/análogos & derivados , Glaucoma/sangue , Pressão Intraocular , Idoso , Arginina/sangue , Biomarcadores/sangue , Estudos Transversais , Feminino , Seguimentos , Glaucoma/diagnóstico , Humanos , Masculino , Índice de Gravidade de Doença
14.
Nitric Oxide ; 109-110: 50-56, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33684543

RESUMO

BACKGROUND: Studies regarding the predictive utility of the blood level of asymmetric dimethylarginine (ADMA) in patients with coronary artery disease (CAD) have yielded the conflicting findings. This meta-analysis sought to evaluate the prognostic value of blood ADMA level in CAD patients. METHODS: Potentially relevant studies were identified by searching PubMed and Embase database until August 12, 2020. Cohort studies evaluating the association of blood ADMA level with all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACEs) were included. A random effect model was applied to pool the multivariable-adjusted risk ratio (RR) and 95% confidence intervals (CI) for the highest versus lowest ADMA level. RESULTS: Data were retrieved from 11 studies enrolling a total of 9496 CAD patients. When compared the highest to the lowest ADMA level, the pooled RR was 2.10 (95% CI 1.46-3.02) for all-cause mortality, 2.49 (95% CI 1.34-4.65) for cardiovascular mortality, and 1.71 (95% CI 1.27-2.32) for MACEs, respectively. However, subgroup analysis showed that there were no significant association between elevated ADMA level and all-cause mortality in acute coronary syndrome (RR 2.11; 95% CI 0.93-4.78) and follow up ≤ 1 year (RR 2.15; 95% CI 0.56-8.25) subgroup. CONCLUSIONS: Elevated blood ADMA level is possibly an independent predictor of all-cause mortality, cardiovascular mortality, and MACEs in CAD patients. Measurement of blood level of ADMA may improve risk classification of CAD. However, these findings should be interpreted with caution because of the limited number of studies included.


Assuntos
Arginina/análogos & derivados , Doença da Artéria Coronariana/diagnóstico , Arginina/sangue , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Humanos , Prognóstico
15.
BMC Cardiovasc Disord ; 21(1): 125, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33663396

RESUMO

BACKGROUND: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. METHODS: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. RESULTS: Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34%, p = 0.018), preoperative AFib (43 vs. 16%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m2, p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm2, p = 0.005) and reduced LVEF (50 vs. 55%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75-6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12-5.73, Euro Score II (OR 1.34, CI 1.02-1.78), preoperative AF (OR 4.86, CI 2.06-11.47), GFR (OR 7.72, CI 1.87-31.96), albumin (OR 1.56, CI 0.52-2.60), Pentraxin-3 (OR 19.68, CI 14.13-25.24), depressed LVEF (OR 8.61, CI 6.37-10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40-4.29 and pCa 5.2; OR 2.00, CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. CONCLUSIONS: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.


Assuntos
Cálcio/metabolismo , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Contração Miocárdica , Miofibrilas/metabolismo , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita , Idoso , Arginina/análogos & derivados , Arginina/sangue , Doenças Assintomáticas , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albumina Sérica Humana/metabolismo , Componente Amiloide P Sérico/metabolismo , Resultado do Tratamento , Disfunção Ventricular Direita/sangue , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologia
16.
BMC Pulm Med ; 21(1): 91, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731064

RESUMO

BACKGROUND: Silicosis is a progressive pneumoconiosis characterized by interstitial fibrosis following exposure to silica dust. The role of metabolic dysregulation in the pathogenesis of silicosis has not been investigated in detail. This study aimed to identify different metabolic features in the plasma of patients with silicosis and dust-exposed workers without silicosis in metabolomics studies. METHODS: Patients with silicosis, dust-exposed workers (DEWs) without silicosis and age-matched healthy controls were recruited in a case-control study. The metabolomics analyses by ultra-high performance liquid chromatography-mass spectrometry were conducted. Distinct metabolic features (DMFs) were identified in the pilot study and were validated in the validation study. The enriched signalling pathways of these DMFs were determined. The ability of DMFs to discriminate among the groups was analysed through receiver operating characteristic (ROC) curves. The correlations between DMFs and clinical features were also explored. RESULTS: Twenty-nine DMFs and 9 DMFs were detected and had the same trend in the pilot study and the validation study in the plasma of the DEW and silicosis groups, respectively. Sphingolipid metabolism was the major metabolic pathway in the DEWs, and arginine and proline metabolism was associated with silicosis. Twenty DMFs in the DEWs and 3 DMFs in the patients with silicosis showed a discriminatory ability with ROC curve analysis. The abundance of kynurenine was higher in Stage III silicosis than in Stage I or Stage II silicosis. L-arginine and kynurenine were both negatively correlated with the percentage of forced vital capacity predicted in silicosis. CONCLUSIONS: Distinct metabolic features in the plasma of DEWs and the patients with silicosis were found to be different. Sphingolipid metabolism and arginine and proline metabolism were identified as the major metabolic pathway in the DEW and silicosis groups, respectively. L-arginine and kynurenine were correlated with the severity of silicosis.


Assuntos
Arginina/sangue , Cinurenina/sangue , Prolina/sangue , Silicose/sangue , Esfingolipídeos/sangue , Idoso , Estudos de Casos e Controles , China , Poeira , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , Projetos Piloto , Curva ROC , Silicose/diagnóstico , Silicose/fisiopatologia , Capacidade Vital
17.
PLoS One ; 16(2): e0247049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33596230

RESUMO

Symmetric dimethylarginine (SDMA) is a promising renal marker that correlates well with the glomerular filtration rate and could allow earlier detection of impaired renal function. The main objectives of this study were to assess the long-term variability of SDMA in healthy dogs and examine the influence of an increased body fat percentage on the level of SDMA. Sixteen lean Beagles were randomly assigned to the control group or weight-change group in age- and gender-matched pairs. The energy intake of the control group (n = 8) was strictly regulated to maintain an ideal body weight for 83 weeks, while the weight-change group (n = 8) was fed to induce weight gain (week 0-47), to maintain stable excessive body weight (week 47-56) and to lose weight (week 56-83), consecutively. At 8 specified time points, the body condition score, body composition, glomerular filtration rate, serum concentration of SDMA and creatinine were analyzed. In the control group, the within-subject coefficient of variation, between-subject coefficient of variation, reference change value (type I error = 5%) and index of individuality were 0.16, 0.22, 0.43 and 0.73, respectively. The control group and weight-change group did not differ significantly in SDMA concentration. SDMA showed a significant negative association (coefficient = -0.07) with body fat percentage (p<0.01) in the weight-change group and a significant positive association (coefficient = 7.79) with serum creatinine (p<0.01) in the entire study population. In conclusion, SDMA concentration has high long-term stability in healthy adult dogs. For the evaluation of SDMA concentrations, subject-specific reference values are preferred over a population-based reference value seen their higher sensitivity. Moreover, an increased body fat percentage does seem to affect the serum SDMA concentration of otherwise healthy dogs, but its clinical relevance has to be clarified in further research.


Assuntos
Arginina/análogos & derivados , Biomarcadores/sangue , Composição Corporal/fisiologia , Tecido Adiposo/metabolismo , Animais , Arginina/sangue , Creatinina/sangue , Doenças do Cão/sangue , Cães , Feminino , Taxa de Filtração Glomerular/fisiologia , Masculino
18.
Lab Invest ; 101(7): 808-823, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33574439

RESUMO

Dimethylarginine dimethylamino hydrolase-1 (DDAH-1) is an important regulator of nitric oxide (NO) metabolism that has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, its role in cerebral ischemia still needs to be elucidated. Herein, we examined the expression of DDAH-1 in the brain of rat by double-label immunofluorescence staining. DDAH-1 knock-out (DDAH-1-/-) and wild-type rats underwent middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, neurological scores, TTC staining and TUNEL assay were used to evaluate neurological damages. 3 and 7-days infarct outcomes were also shown. Blood-brain-barrier (BBB) permeability was examined via Evans blue extravasation and tight junction (TJ) proteins expression and mRNA levels by western blot and RT-qPCR. The levels of plasma asymmetric dimethylarginine (ADMA), NO and ADMA in brain tissue were also assessed. In addition, supplementation of L-arginine to DDAH-1-/- rats was used to explore its role in regulating NO. DDAH-1 was abundantly distributed in cerebral cortex and basal nuclei, and mainly expressed in neurons and endothelial cells. DDAH-1-/- rats showed aggravated neurological damage and BBB disruption, including decrease of TJ proteins expression but indistinguishable mRNA levels after MCAO/R. DDAH-1 depletion and neurological damages were accompanied with increased ADMA levels and decreased NO concentrations. The supplementation with L-arginine partly restored the neurological damages and BBB disruption. To sum up, DDAH-1 revealed to have a protective role in ischemia stroke (IS) and IS-induced leakage of BBB via decreasing ADMA level and possibly via preventing TJ proteins degradation.


Assuntos
Amidoidrolases , Arginina/análogos & derivados , Barreira Hematoencefálica/fisiopatologia , Isquemia Encefálica/fisiopatologia , Amidoidrolases/genética , Amidoidrolases/metabolismo , Animais , Arginina/sangue , Arginina/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Masculino , Óxido Nítrico/sangue , Óxido Nítrico/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos
19.
Acta Biochim Pol ; 68(1): 143-149, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33543609

RESUMO

INTRODUCTION: Patients with type 2 diabetes represent 50% of all sudden cardiac deaths. Disseminated arteriosclerotic lesions are the cause of vascular incidents that cause permanent disability resulting from lower limb amputations. OBJECTIVES: Our study was designed to investigate the relationship between asymmetrical dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) plasma concentration and intima-media thickness (IMT) in subjects with diabetes mellitus without vascular complications (group A) and a group of diabetic patients diagnosed with diabetes micro- and macroangiopathy (group B). PATIENTS AND METHOD: The experimental groups included 42 diabetic patients. Group A - 22 patients (9 W and 13 M), free from vascular complications (mean age 55.83±7.37 years), group B - 20 patients (6 W, 14 M) with accompanying micro- and macropathic changes (mean age 63.80±8.79 years). Group C (n=22), the control group, consisted of healthy volunteers (12 W and 10 M), between the ages of 40 to 60 (mean age 51.16±6.39), selected in reference to the age and sex of the research group. The carotid artery intima-media complex thickness (IMT) was evaluated with the use of a duplex ultrasound. CONCLUSIONS: There was no correlation between ADMA and the maximal or mean intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA). We demonstrated a correlation between symmetric dimethylarginine (SDMA) concentration and CCA IMT. The results suggest that ICA IMT may serve as a marker of vascular complication among patients with diabetes.


Assuntos
Arginina/análogos & derivados , Aterosclerose/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/complicações , Adulto , Idoso , Arginina/sangue , Aterosclerose/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Doença Crônica , Angiopatias Diabéticas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ultrassonografia Doppler em Cores/métodos
20.
Nutr Metab Cardiovasc Dis ; 31(3): 939-949, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33549429

RESUMO

BACKGROUND AND AIMS: There is some promising evidence regarding the beneficial effect of coconut oil on cardiometabolic risk factors. This study aimed to assess the effects of virgin coconut oil (VCO) consumption on metabolic syndrome (MetS) components, as well as, asymmetric dimethylarginine (ADMA) in adults with MetS. METHODS AND RESULTS: In this randomized controlled trial, 48 subjects, aged 20-50 years, with MetS were allocated into two groups; the intervention group was given 30 ml of VCO per day to substitute the same amounts of fat in their usual diet for four weeks. The control group was advised to follow their usual diet. VCO consumption significantly reduced serum levels of triglyceride (TG) (P = 0.001), very low-density lipoprotein (VLDL) (P = 0.001), and fasting blood sugar (FBS) (P = 0.015) compared to the control group. The levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) were significantly increased in the VCO group when compared to the control group (P = 0.001). Circulatory ADMA also increased in the VCO group compared to the control group (P = 0.003). No significant differences were observed in the LDL-C/HDL-C ratio, anthropometric parameters, and blood pressure measurements between the two groups at the end of the study (P > 0.05). CONCLUSION: VCO consumption increased the values of HDL-C while reduced TG and FBS levels. Blood pressure and waist circumference did not change. However, levels of TC, LDL-C, and ADMA elevated by VCO consumption. Caution is warranted until the results of further studies become available to explain the long-term effects of VCO consumption. REGISTRATION NUMBER: IRCT20131125015536N11.


Assuntos
Arginina/análogos & derivados , Glicemia/metabolismo , Óleo de Coco/administração & dosagem , Gorduras na Dieta/administração & dosagem , Lipídeos/sangue , Síndrome Metabólica/sangue , Adulto , Arginina/sangue , Biomarcadores/sangue , Óleo de Coco/efeitos adversos , Gorduras na Dieta/efeitos adversos , Feminino , Humanos , Irã (Geográfico) , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
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