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1.
Adv Clin Exp Med ; 29(1): 91-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32017477

RESUMO

BACKGROUND: Advanced glycation end-products (AGEs) are formed during cascade reactions between reducing sugars or reactive aldehydes and proteins, lipids or DNA molecules. They constitute a group of various stable compounds. Advanced glycation end-products are considered potential biomarkers of metabolic disorders. However, so far only a few methods to determine the level of individual AGEs have been developed. OBJECTIVES: The aim of the study was to compare the efficiency of the slot-dot blot method and direct enzyme-linked immunosorbent assay (ELISA) in detecting non-standard epitopes of methylglyoxal (MGO)-modified proteins (AGE4) found in diabetes serum in trace amounts, and to assess AGE4 in diabetes and associated metabolic abnormalities. MATERIAL AND METHODS: The presence of AGE4 was detected using 2 methods: direct ELISA and the slot-dot blot method - a newly developed immunoassay based on monoclonal, commercially available antibody detection of non-standard AGE epitopes. AGE4 quantification, expressed as median AGE4 in arbitrary units (AU) and AGE4 positivity (the percent of samples with detectable AGE4) was related to diabetes-associated metabolic abnormalities, complications and treatment. RESULTS: Slot-dot blot was significantly more efficient than ELISA in detecting non-standard AGE4 epitopes. AGE4 positivity was less frequent in patients with microangiopathy and in those with polyneuropathy. In patients with abnormal glucose metabolism, metformin treatment was associated with higher AGE4. AGE4 positivity was significantly lower in gliptin-treated patients. Multivariate analysis showed that polyneuropathy and obesity were independently associated with AGE4 positivity, with odds ratios (ORs) of 0.21 and 3.02, respectively. Moreover, logistic regression showed that AGE4 positivity and HbA1c are independent predictors of polyneuropathy. Considering both indicators allows correct classification of 70.4% of cases with a general accuracy of 76%. CONCLUSIONS: The slot dot-blot method detects compounds found in serum in trace amounts. Accumulation of AGE4 was associated with glucose metabolism abnormalities. A tendency toward AGE4 positivity was less frequent in patients with microangiopathy and in non-treated and gliptin-treated diabetes patients.


Assuntos
Epitopos , Produtos Finais de Glicação Avançada , Obesidade , Polineuropatias , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/genética , Humanos , Imunoensaio , Obesidade/genética , Polineuropatias/genética
2.
BMC Infect Dis ; 19(1): 1039, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31818258

RESUMO

BACKGROUND: Ligands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated. METHODS: We examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC). RESULTS: Systemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens. CONCLUSIONS: Our data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy.


Assuntos
Antígenos de Neoplasias/sangue , Diabetes Mellitus/tratamento farmacológico , Metformina/uso terapêutico , Proteínas Quinases Ativadas por Mitógeno/sangue , Proteína S100A12/sangue , Tuberculose Pulmonar/sangue , Adulto , Idoso , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Comorbidade , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Produtos Finais de Glicação Avançada/sangue , Proteína HMGB1/sangue , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Regulação para Cima
3.
Acta Diabetol ; 56(12): 1323-1331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494747

RESUMO

AIMS: Nephropathic patients show higher levels of advanced glycation end products (AGEs) and oxidized human serum albumin (HSAox) compared to healthy subjects. These two classes of compounds are formed as the result of oxidative insults; for this reason, they can be useful oxidative stress biomarkers. The present study examines the variation of AGEs and HSAox in hemodialysis (HD) patients before and after dialysis session, evaluating the impact of different dialytic techniques and filters on their removal. METHODS: A total of 50 healthy subjects (control group) and 130 HD patients were enrolled in the study. Hemodialysis patients were subdivided based on dialytic techniques: 109 in diffusive technique and 22 in convective technique. We monitored HSAox, AGEs and other laboratory parameters at early morning in healthy subjects and in HD patients before and after the dialysis procedures. RESULTS: The level of HSAox decreases after a single dialytic session (from 58.5 ± 8.8% to 41.5 ± 11.1%), but the concentration of total AGEs increases regardless of adopted dialytic techniques (from 6.8 ± 5.2 µg/ml to 9.2 ± 4.4 µg/ml). In our study, levels of HSAox and total AGEs are similar in diabetic and non-diabetic HD patients. The increase in total AGEs after dialysis was only observed using polysulfone filters but was absent with polymethacrylate filters. CONCLUSIONS: HSAox is a simple and immediate method to verify the beneficial effect of a single dialysis session on the redox imbalance, always present in HD patients. Total AGEs assayed by ELISA procedure seem to be a less reliable biomarker in this population.


Assuntos
Biomarcadores , Produtos Finais de Glicação Avançada/sangue , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Albumina Sérica Humana/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/fisiologia , Polímeros/química , Ácidos Polimetacrílicos/química , Prognóstico , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Albumina Sérica Humana/análise , Sulfonas/química , Resultado do Tratamento
4.
Nutr Metab Cardiovasc Dis ; 29(10): 1050-1060, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31371263

RESUMO

AIMS: This work aimed to compare the behavior of the advanced glycation end products (AGEs) and their soluble receptor (sRAGE) in two cohorts of patients: those with heart failure (HF) and acute coronary syndrome (ACS). METHODS AND RESULTS: A unicentric observational clinical study was performed in 102 patients with ACS and 102 patients with chronic HF matched by age and gender. At inclusion, fluorescent AGEs were measured by quantitative fluorescence spectroscopy of plasma, and total sRAGE and endogenous secretory RAGE (esRAGE) levels were determined by enzyme-linked immunosorbent assay kits. A 5-year follow-up period was established for recording cardiac death (primary endpoint) and the incidence of non-fatal myocardial infarction or HF readmission (secondary endpoints). Higher glycation parameters were observed in HF patients, whereas no differences in sRAGE forms were found between HF and ACS cohorts, except for cRAGE, which was higher in HF. Associations between glycation parameters and sRAGE forms were observed in HF, but not in ACS. Differences were also evidenced in the long-term prognosis of each cohort: esRAGE showed an independent prognostic value for cardiac death or non-fatal cardiovascular events in HF, but none of the AGE-RAGE variables were predictors in ACS. CONCLUSIONS: A different role for the AGE-RAGE axis was observed in HF and ACS. All the sRAGE forms were directly related with glycation parameters in HF, but not in ACS. The independent value of the sRAGE forms on each cardiovascular disease was supported by esRAGE being an independent predictor of bad long-term prognosis only for HF.


Assuntos
Síndrome Coronariana Aguda/sangue , Produtos Finais de Glicação Avançada/sangue , Insuficiência Cardíaca/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Progressão da Doença , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Espanha , Fatores de Tempo
5.
Diabetes Metab Syndr ; 13(4): 2457-2461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405660

RESUMO

AIM: To evaluate the role of advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) expression levels as predictors of vascular complications in uncontrolled type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional study was conducted on T2DM adults of both sexes who attended the outpatient service of Al-Karak Teaching Hospital, Jordan during the period from June 2017 to August 2018. Participants were categorized in two groups according to their glycemic control and the presence of reno-vascular complications. Twenty healthy subjects were recruited as control group. Blood sample was obtained from all participants and used for the assessment of FBG, HbA1c, serum AGEs and sRAGE, serum urea and creatinine; 24 h urine was also collected for the determination of urinary albumin. RESULTS: Diabetic subjects with vascular complication had a significantly higher serum AGEs 50.3 ±â€¯13 vs. 28.9 ±â€¯8 pg/ml) and AGEs/sRAGE ratio (0.058 ±â€¯0.02 vs. 0.037 ±â€¯0.02) associated with significantly lower serum sRAGE (868.7 ±â€¯50.8 vs. 912.8 ±â€¯294.3) compared to those with no complications. Serum AGEs and sRAGE showed weak negative and non-significant association in both groups of patients. However, the AGEs/sRAGE ration was inversely and significantly associated with the urinary albumin/creatinine ratio (r = - 0.51, P = 0.009) only in DM patients with reno-vascular complications. CONCLUSION: We found an association between AGEs/sRAGE ratio and urinary albumin/serum creatinine ratio in T2DM patients with reno-vascular complications; providing evidence that serum AGEs and sRAGE can be considered as predictors of vascular complications in uncontrolled T2DM patients.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Glicemia/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Cells ; 8(8)2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31426413

RESUMO

We investigated the correlation of the soluble receptor for advanced glycation end products (sRAGE) and endogenous secretory RAGE (esRAGE) with markers of cardiovascular disease in subjects with normal glucose tolerance (NGT) and 1 h postload glucose ≥155 mg/dL after an oral glucose tolerance test. We stratified 282 subjects without a previous diagnosis of diabetes into three groups: 123 controls (NGT and 1 h postload glycemia <155 mg/dL), 84 NGT and 1 h postload glycemia ≥155 mg/dL (NGT 1 h high), and 75 subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT). NGT 1 h high subjects exhibited lower esRAGE (0.36 ± 0.18 vs. 0.4 5 ± 0.2, p < 0.05) and higher S100A12 levels than controls (5684 (3193.2-8295.6) vs. 3960.1 (2101.8-7419), p < 0.05). Furthermore, they showed an increased pulse wave velocity (PWV) and intima-media thickness (IMT). No differences were found between the NGT 1 h high group and the IFG/IGT group regarding cardiometabolic profiles. After multiple regression analyses, esRAGE was associated with glycated hemoglobin (HbA1c) and high-sensitivity C-reactive protein (hs-CRP). Age, HbA1c, and esRAGE were the determinants of IMT, whereas S100A12 and systolic pressure were the determinants of PWV. The NGT 1 h high group exhibited low esRAGE levels and an altered cardiometabolic profile. HbA1c, S100A12, and hs-CRP were associated with these alterations. In conclusion, subjects with NGT are not a homogeneous population, and they present different cardiovascular and glycometabolic risks.


Assuntos
Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina A Glicada/análise , Receptor para Produtos Finais de Glicação Avançada/sangue , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diagnóstico Precoce , Intolerância à Glucose/complicações , Produtos Finais de Glicação Avançada/sangue , Humanos , Pessoa de Meia-Idade , Estado Pré-Diabético , Fatores de Risco
7.
Diabetes Metab Syndr ; 13(2): 1005-1010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336435

RESUMO

BACKGROUND: While hyperglycemia has a key role in the pathogenesis of microvascular complications of diabetes, it is just one of the many factors contributing to macrovascular damage. The aim of the present study is to investigate the link between serum pentosidine and sRAGE levels and vascular complications in patients with prediabetes compared to normal glucose tolerance controls with obesity. METHODS: In this study were included 76 patients with mean age 50.7 ±â€¯10.7 years, divided into two age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n = 38) and group 2 with obesity and prediabetes (n = 38). RESULTS: There was no significant difference in pentosidine and sRAGE levels between patients with obesity and prediabetes. Patients with hypertension had lower levels of sRAGE compared to nonhypertensive subjects. sRAGE showed a weak negative correlation to blood glucose on 60th min of OGTT and HOMA index. There was no correlation between sRAGE and pentosidine levels and the markers of micro- and macrovascular complications. There was no difference in sRAGE and pentosidine levels between patients with and without endothelial dysfunction. CONCLUSIONS: sRAGE and pentosidine levels are similar in patients with obesity with and without prediabetes and do not correlate to the markers of micro- and macrovascular complications.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Produtos Finais de Glicação Avançada/sangue , Obesidade/fisiopatologia , Estado Pré-Diabético/complicações , Receptor para Produtos Finais de Glicação Avançada/sangue , Adulto , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico
8.
Medicine (Baltimore) ; 98(30): e16573, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348288

RESUMO

RATIONALE: Previous studies have suggested that increased levels of advanced glycation end products (AGEs) and soluble receptor for AGE (sRAGE) are associated with diabetes-related complications. However, there is little evidence on the association between long-term levels of AGEs and sRAGE and progression of diabetes-related complications. PATIENT CONCERNS: A 64-year-old man had poorly controlled type 2 diabetes, obesity, smoking, hypertension, and dyslipidemia. He had many risk factors for diabetes-related complications. DIAGNOSIS: Despite poor glycemic control over 15 years, the patient did not exhibit diabetes-related complications. INTERVENTIONS: We examined serum AGEs (CEL and MG-H1) and sRAGE levels in this patient over the past 10 years. OUTCOMES: The patient maintained low serum AGEs and sRAGE levels. LESSONS: AGEs and sRAGE levels may be associated with long-term development of diabetes-related complications.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Glicemia , Progressão da Doença , Dislipidemias/complicações , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fumar/epidemiologia
9.
Free Radic Res ; 53(8): 841-850, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31234658

RESUMO

Still little is known about the redox abnormalities in patients with non-alcoholic fatty liver disease (NAFLD). The purpose of the study was to find the relationship between enzymatic and non-enzymatic antioxidants, redox homeostasis and oxidative damage in 67-patients with NAFLD. The study population was divided into patients with non-alcoholic fatty liver (early NAFLD, n = 29) and patients with non-alcoholic steatohepatitis (advanced NAFLD, n = 38). Redox biomarkers: enzymatic antioxidants (Cu - Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR)); non-enzymatic antioxidants and redox status (reduced glutathione (GSH), total antioxidant capacity (TAC)); and oxidative damage products (total oxidant status (TOS), advanced glycation end products (AGE), malondialdehyde (MDA), and DNA/RNA oxidative damage) were determined in the serum/plasma samples. The activity of SOD, GPx, GR and levels of GSH, TOS, AGE, MDA, and DNA/RNA oxidative damage were significantly elevated in early NAFLD and advanced NAFLD group compared to controls (p < .001). There was a positive correlation between AGE, TAC and ALT activity (R = 0.34, p = .04; R = 0.36, p = .03, respectively) in advanced NAFLD group. Interestingly, ROC analysis for AGE showed good discriminatory ratio for patients with minimal steatosis (BARD score 0-1) vs. moderate steatosis (BARD score 2-4), AUC = 0.76. Plasma AGE can be a potential non-invasive biomarker differentiating NAFLD patients.


Assuntos
Produtos Finais de Glicação Avançada/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Adulto , Antioxidantes/análise , Biomarcadores/sangue , Catalase/sangue , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Humanos , Masculino , Malondialdeído/análise , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Superóxido Dismutase/sangue
10.
Cell Mol Life Sci ; 76(20): 4103-4115, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31250032

RESUMO

Cardiovascular diseases (CVDs) are among the leading threats to human health. The advanced glycation end product (AGE) and receptor for AGE (RAGE) signaling pathway regulates the pathogenesis of CVDs, through its effects on arterial stiffness, atherosclerosis, mitochondrial dysfunction, oxidative stress, calcium homeostasis, and cytoskeletal function. Targeting the AGE/RAGE pathway is a potential therapeutic strategy for ameliorating CVDs. Vitamin D has several beneficial effects on the cardiovascular system. Experimental findings have shown that vitamin D regulates AGE/RAGE signaling and its downstream effects. This article provides a comprehensive review of the mechanistic insights into AGE/RAGE involvement in CVDs and the modulation of the AGE/RAGE signaling pathways by vitamin D.


Assuntos
Cardiomiopatias Diabéticas/prevenção & controle , Produtos Finais de Glicação Avançada/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocardite/prevenção & controle , Receptor para Produtos Finais de Glicação Avançada/genética , Vitamina D/uso terapêutico , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Animais , Cálcio/metabolismo , Cardiotônicos/uso terapêutico , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/sangue , Guanidinas/uso terapêutico , Humanos , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocardite/sangue , Miocardite/genética , Miocardite/patologia , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/sangue , Transdução de Sinais , Tiazóis/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Vitamina D/sangue
11.
J Ethnopharmacol ; 241: 112009, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31158442

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Agriophyllum squarrosum (L.) Moq. is a traditional Mongol medicine commonly used in the treatment of diabetes. AIM OF THE STUDY: To examine the effects of Agriophyllum squarrosum extract (ASE) on glucose metabolism in type 2 diabetic KKAy mice, and to investigate the mechanisms underlying these effects. MATERIAL AND METHODS: KKAy mice were divided into a model control group (MCG), a low-dose Agriophyllum squarrosum extract group (LASEG), a medium-dose Agriophyllum squarrosum extract group (MASEG), a high-dose Agriophyllum squarrosum extract group (HASEG), and a metformin group (MEG). Syngeneic C57BL/6 mice were used as a normal control group (NCG). Drugs were administered to all mice by gavage for 8 weeks. Random blood glucose levels were measured in the mice at baseline and after 2, 4, and 8 weeks of treatment. Glucose tolerance was measured after 6 weeks of drug administration. After 8 weeks, glycated serum proteins (GSP) and advanced glycation end-products (AGEs) in the serum of all mice were measured. Sections of mouse liver tissues were used for periodic acid-Schiff staining (PAS) and the content of hepatic glycogen was determined. Immunohistochemistry was used to determine the effects of ASE on liver phospho-insulin receptor substrate 2 (P-IRS2) protein expression. Western blotting was used to quantify the protein expression levels of phosphatidylinositol 3-kinase (PI3K), AKT, phospho-AKT (S473) (P-AKT), glycogen synthase kinase 3ß (GSK3ß), and glucose transporters 4 (GLUT4), while PCR was used to quantify the mRNA expression levels of insulin receptor substrate 2 (IRS2), PI3K, AKT, GSK3ß, and GLUT4. RESULTS: ASE treatment decreased random blood glucose levels in type 2 diabetic KKAy mice; increased glucose tolerance; decreased serum GSP and AGEs content; increased glycogen synthesis in liver tissues; upregulated the protein expression levels of PI3K, AKT, GLUT4, and P-IRS2; downregulated the protein expression level of GSK3ß in liver tissues; upregulated the mRNA expression levels of IRS2, PI3K, AKT, and GLUT4; and downregulated the mRNA expression level of GSK3ß in liver tissues. CONCLUSION: ASE treatment may increase glucose metabolism in KKAy mice and improve glucose tolerance. The underlying mechanisms of the beneficial effects of ASE may be associated with the increase of glycogen synthesis, the inhibition of AGEs production, the upregulation of IRS2, PI3K, AKT, and GLUT4 protein and mRNA expression, and the downregulation of GSK3ß protein and mRNA expression.


Assuntos
Chenopodiaceae , Diabetes Mellitus Experimental/metabolismo , Glucose/metabolismo , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Animais , Proteínas Sanguíneas/análise , Diabetes Mellitus Experimental/sangue , Modelos Animais de Doenças , Feminino , Produtos Finais de Glicação Avançada/sangue , Glicogênio/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/sangue , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
PLoS One ; 14(5): e0217203, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116778

RESUMO

Skin autofluorescence (AF) has been validated as a tool for estimating tissue advanced glycation end products (AGEs) accumulation and predicting long-term cardiovascular outcomes. However, whether measurements of skin AF could predict renal function decline remains controversial. From April, 2014 to April, 2015, we enrolled 245 subjects with at least two conventional risk factors for coronary artery disease (CAD). All were measured for body height and weight, blood pressure, plasma creatinine level, and skin AF at the start of the study. Baseline demographics and laboratory tests data were obtained by chart reviews and patient interviews. Serial plasma creatinine levels were followed regularly every 6-12 months for 2 years. In a stepwise multivariate linear regression analysis, skin AF, was an independent factor for predicting the relative renal function decline rate after adjustment of multiple covariates (ß = -0.036±0.016; p = 0.03). Subgroups analysis revealed that skin AF was a significant factor for relative renal function decline rate in subgroups of age < 65 years (ß = -0.068±0.024; p = 0.02), male sex (ß = -0.053±0.016; p< 0.01), body mass index≧25 Kg/m2(ß = -0.042±0.021; p = 0.04), and estimated glomerular filtration rate ≥ 60 ml/min/1.73m2(ß = -0.043±0.020; p = 0.04). However, only an interaction between skin AF and age attained significance (p for interaction = 0.04). Skin AF is a useful predictor for renal function decline in patients at increased risk of CAD.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Produtos Finais de Glicação Avançada/sangue , Insuficiência Renal Crônica/complicações , Pele/patologia , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/etiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/patologia , Fatores de Risco , Pele/metabolismo
13.
Nutrients ; 11(5)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075971

RESUMO

Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia that induces other pathologies including diabetic retinopathy and bone disease. Adult Danio rerio (zebrafish) represents a powerful model to study both glucose and bone metabolism. Then, the aim of this study was to evaluate the effects of liquiritigenin (LTG) on blood glucose level and diabetes complications in hyperglycemic adult zebrafish. LTG is a flavonoid extracted from Glycyrrhiza glabra roots which possess important antioxidant, anti-inflammatory, and anti-diabetic properties. During four weeks of glucose treatment, LTG significantly prevented the onset of the hyperglycemia in adult zebrafish. Moreover, hyperglycemic fish showed increased advanced glycation end-products (AGEs) and parathormone levels whereas LTG completely prevented both of these metabolic alterations. Large bone-loss areas were found in the scales of glucose-treated fish whereas only small resorption lacunae were detected after glucose/LTG treatment. Biochemical and histological tartrate resistant acid phosphatase (TRAP) assays performed on explanted scales confirmed that LTG prevented the increase of osteoclastic activity in hyperglycemic fish. The osteoblastic alkaline phosphatase (ALP) activity was clearly lost in scales of glucose-treated fish whereas the co-treatment with LTG completely prevented such alteration. Gene expression analysis showed that LTG prevents the alteration in crucial bone regulatory genes. Our study confirmed that LTG is a very promising natural therapeutic approach for blood glucose lowering and to contrast the development of bone complications correlated to chronic hyperglycemia.


Assuntos
Glicemia/metabolismo , Reabsorção Óssea/prevenção & controle , Osso e Ossos/efeitos dos fármacos , Flavanonas/uso terapêutico , Glycyrrhiza/química , Hiperglicemia/prevenção & controle , Fitoterapia , Fosfatase Alcalina/metabolismo , Animais , Reabsorção Óssea/etiologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/prevenção & controle , Modelos Animais de Doenças , Flavanonas/farmacologia , Expressão Gênica , Produtos Finais de Glicação Avançada/sangue , Hiperglicemia/sangue , Hiperglicemia/complicações , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Fosfatase Ácida Resistente a Tartarato/metabolismo , Peixe-Zebra
14.
J Acquir Immune Defic Syndr ; 81(2): e55-e62, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095008

RESUMO

OBJECTIVE: To compare levels of advanced glycation end products (AGEs) between HIV-infected patients and uninfected controls and assess the relationship between AGEs, HIV, inflammation, and endothelial dysfunction. DESIGN: Cross-sectional study involving 90 individuals (68 HIV+ and 22 healthy controls matched by age and sex). METHODS: AGE levels were assessed using 3 different modalities: free AGEs were measured in the serum, skin autofluorescence (AF) was determined with a noninvasive reader, and dietary AGEs were estimated using 24-hour dietary recalls. Markers of inflammation, immune activation, and endothelial dysfunction were also measured. Wilcoxon rank-sum and χ tests were used to compare AGEs between groups. Spearman correlations were used to explore relationships between variables while adjusting for different covariates. RESULTS: Overall, 71% were men and 68% were African American, with a median age of 53 years. Among HIV-infected individuals, all participants were on antiretroviral therapy by design, and most participants (78%) had an undetectable HIV-1 RNA level (≤20 copies/mL). Skin AF and serum AGEs were significantly higher in HIV-infected participants compared with uninfected controls (P < 0.01), whereas no differences in dietary AGEs were found between groups (P = 0.2). In the HIV-infected group, but not in controls, skin AF and circulating AGEs were significantly associated with inflammatory and oxidative markers, and with markers of endothelial dysfunction. CONCLUSIONS: These results suggest intrinsic production of AGE in HIV-infected individuals. The relationship between serum/skin AGE and inflammatory, oxidative, and cardiovascular markers highlights the potential implications of AGEs in chronic inflammation and endothelial dysfunction in HIV, suggesting a new potential target for HIV-associated heightened inflammation and cardiovascular risk.


Assuntos
Células Endoteliais/imunologia , Produtos Finais de Glicação Avançada/imunologia , Infecções por HIV/complicações , Inflamação/complicações , Inflamação/imunologia , Antirreumáticos/uso terapêutico , Biomarcadores/sangue , Sistema Cardiovascular , Estudos Transversais , Dieta , Feminino , Produtos Finais de Glicação Avançada/sangue , Produtos Finais de Glicação Avançada/metabolismo , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Estresse Oxidativo , Pele/imunologia
15.
Diab Vasc Dis Res ; 16(5): 483-485, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31064218

RESUMO

Carboxymethyl-lysine is an advanced glycation end product that is detectable in the serum. Higher carboxymethyl-lysine levels have been associated with increased risk of coronary heart disease, stroke and cardiovascular mortality. We determined whether high carboxymethyl-lysine levels are also associated with the risk of peripheral artery disease in Cardiovascular Health Study participants who were all aged 65 years and older at baseline. Multivariate Cox proportional hazards models were used to determine the association of baseline carboxymethyl-lysine levels with incident peripheral artery disease in 3267 individuals followed for a median length of 10.0 years. A total of 157 cases of incident peripheral artery disease occurred during follow-up. No significant relationship between carboxymethyl-lysine and risk of peripheral artery disease was found (hazard ratio per standard deviation increment = 1.03; 95% confidence interval = 0.87, 1.23).


Assuntos
Produtos Finais de Glicação Avançada/sangue , Lisina/análogos & derivados , Doença Arterial Periférica/sangue , Doença Arterial Periférica/epidemiologia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Incidência , Lisina/sangue , Masculino , Doença Arterial Periférica/diagnóstico , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
16.
Diab Vasc Dis Res ; 16(5): 458-465, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31046456

RESUMO

AIM: To investigate the thrombotic microenvironment in early stages of type 2 diabetes mellitus measuring platelet-derived, endothelial-derived and erythrocyte-derived microvesicles. METHODS: We recruited 50 newly diagnosed type 2 diabetes mellitus patients who did not receive glucose-lowering treatment except for metformin and 25 matched non-type 2 diabetes mellitus volunteers. Microvesicles were measured with flow cytometry, glycated haemoglobin with high-performance liquid chromatography and advanced glycation end products with enzyme-linked immunosorbent assay. RESULTS: Type 2 diabetes mellitus patients showed significantly higher levels of platelet-derived microvesicles [195/µL (115-409) vs 110/µL (73-150), p = 0.001] and erythrocyte-derived microvesicles [26/µL (9-100) vs 9/µL (4-25), p = 0.007] compared to non-type 2 diabetes mellitus individuals. Platelet-derived microvesicles were positively associated with fasting blood glucose (p = 0.026) and glycated haemoglobin (p = 0.002). Erythrocyte-derived microvesicles were also positively associated with fasting blood glucose (p = 0.018) but not with glycated haemoglobin (p = 0.193). No significant association was observed between platelet-derived microvesicles (p = 0.126) or erythrocyte-derived microvesicles (p = 0.857) and advanced glycation end products. Erythrocyte-derived microvesicles predicted the presence of type 2 diabetes mellitus, independently of platelet-derived microvesicles. CONCLUSION: In newly diagnosed type 2 diabetes mellitus, ongoing atherothrombosis is evident during the early stages as evidenced by increased microvesicles levels. Furthermore, the association with glycemic profile suggests that microvesicles represent not only a novel mechanism by which hyperglycemia amplifies thrombotic tendency in type 2 diabetes mellitus but also early markers of thrombosis highlighting the need for earlier management of hyperglycemia.


Assuntos
Plaquetas/patologia , Micropartículas Derivadas de Células/patologia , Diabetes Mellitus Tipo 2/patologia , Eritrócitos/patologia , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Plaquetas/metabolismo , Estudos de Casos e Controles , Micropartículas Derivadas de Células/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Eritrócitos/metabolismo , Feminino , Hemoglobina A Glicada/metabolismo , Produtos Finais de Glicação Avançada/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Trombose
17.
Biochimie ; 162: 66-76, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30959081

RESUMO

Advanced glycation end-products (AGEs) from non-enzymatic glycation are implicated in several degenerative diseases, including being a crucial contributor in secondary complications of diabetes. This has garnered significant scientific interest in inhibiting agents of AGEs to prevent and remediate disorders arising due to glycation. In the current study, inhibitory effects on AGEs formation were investigated using bio-enzymatically synthesized nanoformulations of gold (AuNPs) and silver (AgNPs) by physiologically important enzyme, ß galactosidase. Human serum albumin, most abundant protein in human blood plasma, was glycated by incubating with glucose leading to AGEs formation. The AGEs formation was significantly minimized with both AuNPs and AgNPs, as confirmed by various biophysical and biochemical techniques. Circular dichroism and Fourier transform infrared spectroscopy further affirmed antiglycation potential of AuNPs and AgNPs. The results were corroborated with thiol group, free lysine and carbonyl content estimation for native, glycated and nanoparticles (NPs) treated samples. Confocal microscopic imaging was performed to exhibit glycation inhibiting potential of the NPs. The inhibition of AGEs was observed to be slightly stronger in case of AgNPs than AuNPs with both exhibiting promising results as potential anti-glycating agents. The study sheds light on potential of non-toxic NPs being utilized as controlling agents against hyperglycemic conditions and diabetes management.


Assuntos
Glicemia/efeitos dos fármacos , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Ouro/farmacologia , Nanopartículas Metálicas , Albumina Sérica Humana/química , Prata/farmacologia , Dicroísmo Circular/métodos , Diabetes Mellitus/tratamento farmacológico , Produtos Finais de Glicação Avançada/sangue , Glicosilação/efeitos dos fármacos , Humanos , Hiperglicemia/tratamento farmacológico , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , beta-Galactosidase/química
18.
Gynecol Endocrinol ; 35(9): 811-814, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30964350

RESUMO

Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study. Plasma VEGFTOTAL was lower in GDM (17.68 ± 1.30 pg/mL) compared to non-GDM (25.69 ± 1.40 pg/mL). VEGF165b, ICAM-1, and AGEs were higher in GDM (9.9 ± 1.4 pg/mL, 201.04 ± 7.85 µg/mL, and 10.40 ± 0.98 µg/mL, respectively) and lower in non-GDM (6.47 ± 0.70 pg/mL, 174.1 ± 7.11 µg/mL, and 4.71 ± 0.39 µg/mL, respectively). Compared to non GDM (0.25 ± 0.02), VEGF RATIO was higher in GDM (0.45 ± 0.04) and correlated with -ICAM-1 (r = 0.375, p < .001) and AGEs (r = 0.199, p < .05). Tertile stratification of VEGF RATIO implied that frequency of GDM increases with increasing tertiles of VEGF RATIO (p for trend <.001). Association of VEGF RATIO with GDM was significant even after adjusting for AGEs (OR = 1.279, CI = 1.118-1.462, p < .0010) but it lost its significance when adjusted for ICAM-1 (OR = 1.006, CI = 0.995-1.017, p = .308). VEGF RATIO plays an important role in GDM in association with vascular inflammation.


Assuntos
Diabetes Gestacional/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Glicemia/análise , Glicemia/metabolismo , Estudos de Casos e Controles , Feminino , Produtos Finais de Glicação Avançada/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Fragmentos de Peptídeos/sangue , Gravidez , Complicações Cardiovasculares na Gravidez/sangue , Isoformas de Proteínas/sangue , Isoformas de Proteínas/química , Fator A de Crescimento do Endotélio Vascular/química , Malformações Vasculares/sangue , Malformações Vasculares/complicações , Adulto Jovem
19.
J Photochem Photobiol B ; 195: 17-26, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035030

RESUMO

Cumulative ultraviolet (UV) exposure is associated with squamous skin cell carcinoma. UV radiation induces oxidative modifications in biomolecules of the skin leading to photocarcinogenesis. Indeed, the cyclobutene pyrimidine dimers and other dimers formed by photoaddition between carbon-carbon bonds also have an important role in the initiation process. However, information on the systemic redox status during these processes is scarce. Thus, we investigated the systemic redox profile in UVB-induced squamous cell carcinoma in mice. Female hairless mice were exposed to UVB radiation (cumulative dose = 17.1 J/cm2). The dorsal skin of these mice developed actinic keratosis (AK) and squamous cell carcinoma (SCC) and presented increased levels of oxidative and nitrosative stress biomarkers (4-hydroxy-2-nonenal and 3-nitrotyrosine), and decreased antioxidant defenses. Systemically, we observed the consumption of plasmatic antioxidant defenses and increased levels of advanced oxidized protein products (AOPP), an oxidative stress product derived from systemic inflammatory response. Taken together, our results indicate that UVB chronic irradiation leads not only to adjacent and tumoral oxidative stress in the skin, but it systemically is reflected through the blood. These new findings clarify some aspects of the pathogenesis of SCC and should assist in formulating better chemoprevention strategies, while avoiding additional primary SCC development and metastasis.


Assuntos
Carcinoma de Células Escamosas/etiologia , Estresse Oxidativo/efeitos da radiação , Neoplasias Cutâneas/etiologia , Raios Ultravioleta , Animais , Catalase/metabolismo , Feminino , Glutationa/metabolismo , Produtos Finais de Glicação Avançada/sangue , Ceratose/etiologia , Malondialdeído/sangue , Camundongos , Camundongos Pelados , Pele/patologia , Pele/efeitos da radiação
20.
PLoS One ; 14(3): e0213991, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870511

RESUMO

INTRODUCTION: The receptor for advanced glycation end products (RAGE) is expressed in normal lungs and is upregulated during infection. AGEs and RAGE cause oxidative stress and apoptosis in lung cells. The objective of this study is to evaluate levels of AGEs and its soluble receptor (sRAGE), and to investigate their relationship with food intake and nutritional status, in a university-affiliated hospital in Brazil. METHODS: Case-control study, from June 2017 to June 2018. AGE (carboxymethyl lysine, CML) and sRAGE were measured from blood samples by Elisa. Nutritional assessment was performed by body mass index, triceps skin-fold thickness, mid-arm circumference, mid-arm muscle circumference, bioelectrical impedance analysis, and food frequency questionnaire. RESULTS: We included in the study 35 tuberculosis (TB) patients and 35 controls. The mean sRAGE levels were higher in TB patients than in controls (68.5 ± 28.1 vs 57.5 ± 24.0 pg/mL; p = 0.046). Among cases that were current smokers, lower sRAGE levels were associated with mortality, evaluated at the end of hospitalization (p = 0.006), and with weight loss (p = 0.034). There was no statistically significant difference in CML levels and diet CML content between cases and controls. Malnutrition was more frequent in cases, but there was no correlation between nutritional parameters and CML or sRAGE levels. CONCLUSIONS: TB patients had higher sRAGE levels than controls, although it is not clear that this difference is clinically relevant. Also, sRAGE was associated with weight loss and mortality.


Assuntos
Antígenos de Neoplasias/sangue , Produtos Finais de Glicação Avançada/sangue , Proteínas Quinases Ativadas por Mitógeno/sangue , Tuberculose Pulmonar/sangue , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional/fisiologia , Estresse Oxidativo , Estudos Prospectivos , Tuberculose Pulmonar/mortalidade , Tuberculose Pulmonar/fisiopatologia , Perda de Peso , Adulto Jovem
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