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OBJECTIVE: Diabetic foot wounds are a relevant diabetes complication and a major health problem. It has been described that propolis has health benefits due to its anti-inflammatory, antioxidant, and support in the healing process. The current study assessed the effect of propolis as an adjuvant in the healing of human diabetic foot ulcers. This was evaluated in a randomized placebo-controlled study of subjects receiving care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca, Chile. RESEARCH DESIGN AND METHODS: Randomized subjects received ambulatory healing treatment for diabetes foot wounds with propolis spray (3%), which was applied to cover the entire wound surface each time it was dressed from week 0 until cicatrization or 8 weeks as a maximum. Two serum samples were taken (day 0 and end of the study) for cytokine and oxidative stress analyses. Also, macro- and microscopy were analyzed in the process of wound healing. RESULTS: The study comprised 31 subjects with type 2 diabetes in treatment for diabetic foot wounds in the Diagnostic and Treatment Centre from the Regional Hospital of Talca. Propolis promotes a reduction of the wound's area by an average of 4 cm2, related to an increase in the connective tissue deposit compared to the control. Also, propolis increased the glutathione (GSH) and GSH/glutathione disulfide (GSSG) ratio (p < 0.02), depleted tumor necrosis factor- (TNF-) α, and increased interleukin- (IL-) 10 levels. Topical propolis did not modify the biochemical parameters in the serum of the studied subjects. CONCLUSIONS: The topical use of propolis turned out to be an interesting therapeutic strategy as an adjuvant in the care of diabetes foot wounds due to its ability to improve and promote healing based on its anti-inflammatory and antioxidant profile. This trial is registered with NCT03649243.
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Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Pé Diabético/tratamento farmacológico , Hospitais , Própole/administração & dosagem , Pele/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Administração Cutânea , Aerossóis , Idoso , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Chile , Citocinas/sangue , Pé Diabético/sangue , Pé Diabético/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Própole/efeitos adversos , Pele/metabolismo , Pele/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Although there is evidence of the benefits of propolis on human health, the vast majority of studies have been conducted using animal models. The present study includes the chemical characterization and clinical evaluation of the effects of the oral administration of propolis solution on the oxidative status and modulation of lipids in a human population in Talca, Chile. Chemical characterization of propolis, total phenol, flavonoids, and total antioxidant capacity were determined by ORAC. Identification of phenols and flavonoids in propolis was assessed by HPLC-DAD. A double-blind, placebo-controlled clinical trial was conducted. Subjects provided informed consent form and the Bioethics Committee of the Universidad de Talca approved protocol. Eligible subjects (n = 67) were randomized in two groups: propolis (n = 35) and placebo (n = 32). All subjects were evaluated at 0 (baseline), 45, and 90 days. In the propolis group, we observed that increases in HDL-c went from 53.9 ± 11.9 to 65.8 ± 16.7 mg/dL (p < 0.001) from baseline to 90 days. Compared to placebo subjects, consumption of propolis induced a net increase in GSH levels (p < 0.0001) and a decrease (p < 0.001) in TBARS levels for the propolis group. Our findings indicate potential benefits of propolis use in human health. The use of propolis appears to have positive effects on oxidative status and improvement of HDL-c, both of which contribute to a reduced risk of cardiovascular disease.
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OBJECTIVE: We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. RESEARCH METHODS: Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. RESULTS: Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P<0.001). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p<0.001; compared to control group). It was also significantly related to inflammation. CONCLUSION: The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases.
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Diabetes Mellitus Tipo 2/genética , Ferritinas/metabolismo , Heme Oxigenase-1/genética , Inflamação/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancer, and oxidative damage is associated with the development of OSCCs. Antioxidants have therefore been proposed for use as chemoprotective agents against different types of cancer. In the present study, the effect of the antioxidant quercetin, administered at doses of 10 and 100 mg/kg/day, was investigated in an experimental murine model of 4-nitroquinoline 1-oxide (4-NQO)-induced carcinogenesis. The survival of the treated animals, the plasmatic levels of reduced glutathione and the type and severity of lesions (according the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front) were assessed. Additionally, the organization of the extracellular matrix was analyzed by carbohydrate and collagen histochemistry, and immunohistochemistry was used to assess the expression of the tumor markers proliferating cell nuclear antigen and mutated p53. The results indicate that, despite the promising effect of quercetin in other studies, this drug is ineffective as a chemoprotective agent against 4-NQO-induced OSCC in mice at the assayed doses.
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Propolis is commercialized in Chile as an antimicrobial agent. It is obtained mainly from central and southern Chile, but is used for the same purposes regardless of its origin. To compare the antimicrobial effect, the total phenolic (TP), the total flavonoid (TF) content and the phenolic composition, 19 samples were collected in the main production centers in the Región del Maule, Chile. Samples were extracted with MeOH and assessed for antimicrobial activity against Gram (+) and Gram (-) bacteria. TP and TF content, antioxidant activity by the DPPH, FRAP and TEAC methods were also determined. Sample composition was assessed by HPLD-DAD-ESI-MS/MS. Differential compounds in the samples were isolated and characterized. The antimicrobial effect of the samples showed MICs ranging from 31.5 to > 1000 µg/mL. Propolis from the central valley was more effective as antibacterial than those from the coastal area or Andean slopes. The samples considered of interest (MIC ≤ 62.5 µg/mL) showed effect on Escherichia coli, Pseudomonas sp., Yersinia enterocolitica and Salmonella enteritidis. Two new diarylheptanoids, a diterpene, the flavonoids pinocembrin and chrysin were isolated and elucidated by spectroscopic and spectrometric means. Some 29 compounds were dereplicated by HPLC-MS and tentatively identified, including nine flavones/flavonol derivatives, one flavanone, eight dihydroflavonols and nine phenyl-propanoids. Propolis from the Región del Maule showed large variation in antimicrobial effect, antioxidant activity and composition. So far the presence of diarylheptanoids in samples from the coastal area of central Chile can be considered as a marker of a new type of propolis.
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Antibacterianos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/análise , Própole/química , Antibacterianos/química , Antioxidantes/química , Chile , Cromatografia Líquida de Alta Pressão , Diarileptanoides/química , Diarileptanoides/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fenóis/química , Fenóis/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologiaRESUMO
Studies concerning oxidative stress (OxE) parameters have increased, mainly because of its important role in cardiovascular diseases and diabetes complications. The main objective of this study was to evaluate iron nutrition status and oxidative stress parameters in subjects that had developed metabolic syndrome (MetS). Subjects from the Research Program of Risk Factors for Cardiovascular Disease (n = 155) were studied (ages ranging from 45 to 65 years old) and classified according to the Adult Treatment Panel III criterion. A blood sample was taken after a 12-h fasting period, and basal glucose, insulin, thiobarbituric acid reactive substances (TBARS), oxidized LDL (oxLDL), heme oxygenase (HO) activity, lipid profile, and iron nutrition status were determined. Eighty-five subjects were classified as MetS, and 70 non-MetS. Individuals with MetS showed higher Fe storage (high levels of ferritin, total body iron and low transferrin receptor), oxLDL, TBARS, and homeostatic model assessment for insulin resistance levels. The MetS group showed high levels of oxidative stress parameters (HO activity, oxLDL, and TBARS). The presence of MetS showed an association with LDL oxidation risk (multiple lineal regression according to sex and age, p < 0.001). High levels of triglycerides (p < 0.001) and waist circumference (p < 0.012) were associated with oxLDL levels, as well as an association between TBARS and oxLDL with ferritin levels. Through logistic regression analyses, the highest quartile of ferritin was associated with a threefold risk of developing MetS compared to the lowest quartile; also, TBARS showed a 21-fold risk for the development of MetS. Finally, elevated levels of oxidative stress parameters such us oxLDL, TBARS, HO, and Fe storage were associated to MetS.
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Ferro/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Estresse Oxidativo/fisiologia , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Jejum/sangue , Feminino , Ferritinas/sangue , Heme Oxigenase (Desciclizante)/sangue , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Lipídeos/sangue , Lipoproteínas LDL/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Cancer is the second cause of death in the world after cardiovascular diseases. Cancer cells acquire capacities not present in normal cells, such as self-sufficiency, resistance to antiproliferative stimuli, evasion of apoptosis, unlimited replication, invasiveness and metastasis. Consequently, it is of major interest to explore and develop molecules with anticancer activity directed to specific targets. In this study, we aimed to evaluate two series of polycyclic quinones: aza-angucyclinone and arylaminopyrimido[4,5-c]isoquinoline-7,10-quinones, in their capacity to inhibit human topoisomerase I (TOP1) and to trigger apoptosis through activation of caspase-3. We evaluated the capacity of the two series of polycyclic quinones to inhibit TOP1, using a DNA supercoiled relaxation assay and their capacity to induce apoptosis through the activation of caspase-3 in HL60 cells. Both series of quinones inhibited TOP1 activity over 50%. When we evaluated the pro-apoptotic capacity of both series of quinones, at therapeutically relevant concentrations, the arylaminoquinones ADPA-1CC (methyl 7-(4-methoxyphenyl)amino-1,3-dimethyl-5,8-dioxo-5,8-dihydroisoquinoline-4-carboxylate), P4 (9-phenylamino-3,4-dihydrophenanthridine-1,7,10(2H)-trione) and the aza-angucyclinone OH-6H (8-hydroxy-2,4-dimethyl-2H,4H-benzo[g]pyrimido[4,5-c]isoquinoline-1,3,7,12-tetraone) increased the caspase-3 activity by approximately 2-fold over the control. The series of the arylaminoquinones and aza-angucyclinones showed differential antiproliferative capacity. We further identified a group of them that showed antiproliferative capacity possibly through inhibition of TOP1 and by activation of caspase-3. This group of molecules may represent a potential pharmacological tool in the treatment against cancer.
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Antraquinonas/farmacologia , Compostos Aza/farmacologia , Caspase 3/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Quinonas/farmacologia , Inibidores da Topoisomerase I/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Células HL-60 , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologiaRESUMO
AIM: To determine risk parameters associated with high values of high sensitive C-reactive protein (hsCRP) in subjects with different glucose fasting levels. METHODS: Anthropometric parameters, arterial pressure, glycemia, lipid profile, uric acid, and hsCRP were studied in a population of 513 individuals between 40 and 65 years. RESULTS: In total, 349 (68.0%) were normoglycemic (NG); 113 (22.0%) had impaired fasting glucose (IFG); and 51 (9.9%) were diabetic subjects. A multivariate linear regression analysis showed that the natural logarithm of hsCRP was associated significantly with glycemia levels (P = 0.009), uric acid (P = 0.001), diastolic blood pressure (P = 0.011), smoking habit (P = 0.021), BMI (P<0.001), and sex (P<0.001). One-third of the NG subjects had high hsCRP levels. A multiple logistic regression analysis showed that sex and BMI were variables related to high levels of hsCRP in subjects with IFG and NG. In NG subjects, uric acid levels were associated with risk of presenting high hsCRP levels and were higher in women than men. In NG women, ROC curves analysis identified a uric acid level of 3.9 mg/dl as a cut-off point to predict a high value of hsCRP. Those individuals with uric acid values higher than 3.9 mg/dl and normal glycemia had 3.5-fold more risk of having hsCRP levels over 3.0 mg/l. CONCLUSIONS: We sustain that high levels of hsCRP are associated with disturbance in carbohydrate metabolism. In addition, we believe that in low cardiovascular risk population, such as NG women, uric acid levels above 3.9 mg/dl might represent a signal of possible pro-inflammatory state and cardiovascular risk.
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Glicemia/metabolismo , Proteína C-Reativa/análise , Metabolismo dos Carboidratos , Transtornos do Metabolismo de Glucose/sangue , Ácido Úrico/sangue , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares , Jejum , Feminino , Humanos , Hipoglicemia , Masculino , Pessoa de Meia-IdadeRESUMO
Un aumento de las enfermedades cardiovasculares (ECV) mundialmente, la existencia de un porcentaje más alto que el promedio nacional de éstas para la región de Maule (Chile), y una atención incrementada en el análisis de factores psicológicos, motivan el análisis del Patrón de Comportamiento Tipo A (PCTA) y la ira respecto de las ECV. Se trabajó con 1007 participantes de 18 a 74 años (ciudadanos de Talca, Chile), mayoritariamente mujeres, quienes respondieron un cuestionario (información socio demográfica, hábitos alimentarios y de estilo de vida), la Escala Retiro de Patrón de Conducta tipo A (ERCTAa), y el Inventario de Ira de Novaco. Se les midió peso, masa corporal, presión arterial y sangre, como factores de riesgo cardiovascular. Los participantes son altamente sedentarios (79.9%), tabáquicos (53.6%), hipercolesterolémicos (44.5%), con sobrepeso (40.7%) y obesidad (32.6%), un cuarto de los cuales presenta hiperglicemia e hipertensión y con PCTA equirepartido según sexo. Es la ausencia de PCTA (ó presencia de PCTB) la que aparece asociada a factores tradicionales de riesgo cardiovascular (FRCV). La ira alta se presenta más en mujeres que en hombres (2.1% vs. 0.3%; c²(3) = 27.99, p<.0001), disminuyendo para ambos sexos con la edad, pero los infartos acaecen igualmente según sexo.
A worldwide raise in the number of cardiovascular disease (CVD) and the existence of a higher percentage in Maule (Chile) than the national media, and increased attention in the analysis of psychological factors motivate to analyze the Type A Behavior Pattern (TABP) and anger in relation to CVD. The sample was 1007 adults between 18 and 74 years old (citizens of Talca, Chile), mostly women. They provided information about their demographic details, eating habits and lifestyle, answered the Novaco's Anger Inventory and the Retiro Scale of Type A Behavior (RSTAB), and also were taken measurements like weight, body mass index and blood pressure and blood tests related to risk factors to traditional cardiovascular diseases. The results show Overall, that the participants appear highly sedentary (79.9%) with relatively high levels of tabaquism (53.6%), and hypercholesterolemia (44.5%), overweight (40.7%) and obesity (32.6%). A quarter of the sample also presents hyperglycemic indexes, hypertension and TABP unequally distributed by sex. The absence of PCTA (or PCTB presence) appeared mostly associated with traditional cardiovascular risk factors (CRF). Regarding anger, women present more high than men (2.1% against 0.3%; c²(3) = 27.99, p<.0001), decreasing for both sexes with age, while also befall stroke by sex.
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The metabolic syndrome (MS) is a cluster of pathophysiological alterations that includes the presence of hypertension, insulin resistance, dyslipidemia, and abdominal obesity. MS is associated with increased risk of developing diabetes and cardiovascular diseases. Endothelial dysfunction with impaired nitric oxide (NO) bioavailability has been implicated in insulin resistance and hypertension. NO is synthesized by nitric oxide synthase (NOS) using l-arginine as substrate. Asymmetric dimethyl arginine (ADMA) is a major and potent endogenous NOS inhibitor, associated with cardiovascular and renal diseases. We tested the hypothesis that plasmatic ADMA levels are increased in patients with MS. We studied 85 adult individuals from Talca, Chile, separated in two groups, 48 individuals with MS (according to modified ATP III criteria), and 37 individuals without MS as controls. ADMA levels were significantly increased in the MS group (mean±standard deviation 0.71±0.38 vs. 0.48±0.28µmol/L, p=0.0009). Furthermore, the levels of ADMA were modestly but significantly correlated with waist circumference (p=0.01) but not with the other components of MS (blood pressure, glycemia, triglycerides and high density lipoprotein cholesterol HDL-c). These results suggest a possible link between increased ADMA levels and the MS.