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1.
Medicine (Baltimore) ; 98(39): e17298, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574854

RESUMO

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.


Assuntos
Doenças Cardiovasculares , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2 , Haptoglobinas , Adulto , Biomarcadores/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Haptoglobinas/análise , Haptoglobinas/genética , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
2.
Medicine (Baltimore) ; 98(36): e17013, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490384

RESUMO

It is not completely clear whether "the lower, the better" cholesterol hypothesis for cardiovascular disease (CVD) and ischemic heart disease (IHD) can be applied to general populations with a low risk of heart disease mortality.We prospectively followed up 503,340 Koreans who participated in routine health checkups during 2002-2003 until 2013 via linkage to national mortality records.Nonlinear associations with total cholesterol (TC) were found: U-curves for overall CVD (I00-I99; nadir at 180-200 mg/dL) and a reverse-L-curve for IHD (I20-I25). Assuming a linear association in the lower range (<200 mg/dL), TC was inversely associated with CVD mortality (HR per 39 mg/dL [1 mmol/L] increase = 0.90). In the upper range (200-349 mg/dL), TC was positively associated with CVD mortality, largely due to IHD (HR = 1.19), especially acute myocardial infarction (HR = 1.23). The associations were generally similar in men versus women and in middle-aged (40-64 years) versus elderly (≥65 years) adults.TC levels of 180-200 mg/dL were associated with the lowest CVD mortality. Below 200 mg/dL, TC had no graded positive associations with IHD mortality. It remains unclear whether the lowest cholesterol levels are associated with the least mortality from CVD and IHD in Korean adults with a low risk of heart disease.


Assuntos
Colesterol/sangue , Isquemia Miocárdica/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Estudos Prospectivos , República da Coreia/epidemiologia
3.
Chem Biol Interact ; 312: 108819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499052

RESUMO

Cannabidiol (CBD), a compound obtained from Cannabis sativa, has wide range of therapeutic properties, including mitigation of diabetes and neurodegeneration. Cerebral ischemia and consequent learning disabilities are aggravated in elderly diabetic subjects. However, there are no studies showing the effect of CBD treatment in elderly diabetes patients suffering cerebral ischemia. The present work tested the hypothesis that CBD treatment improves metabolic dysfunctions in middle-aged diabetic rats submitted to chronic cerebral hypoperfusion. In this work, 350-day-old male Wistar streptozotocin-induced diabetic rats were used. To induce cerebral ischemia was used a chronic cerebral hypoperfusion (CCH), surgically, via the four-vessel occlusion/internal carotid artery (4-VO/ICA). Four diabetic groups were established: Non-CCH Treated Diabetic (DNT), CCH Treated Diabetic (DCT), Non-CCH Vehicle Diabetic (DNV), and CCH Vehicle Diabetic (DCV). Vehicle groups were not treated with CBD. The animals were treated during 30 days with 10 mg CBD/Kg bw/day. After treatment, the animals were euthanized, and blood levels of glucose, insulin, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fructosamine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were evaluated. DCT group presented reduction of hyperglycemia and an increase of insulinemia. Also was observed lower fructosamine, LDL, HDL, triglycerides and total cholesterol levels. AST and ALT concentration were reduced in CBD treated groups. CBD may be used as therapeutic tool to protect metabolism against injuries from diabetes aggravated by cerebral ischemia.


Assuntos
Isquemia Encefálica/patologia , Canabidiol/uso terapêutico , Diabetes Mellitus Experimental/patologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Isquemia Encefálica/complicações , Colesterol/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Insulina/sangue , Masculino , Ratos , Ratos Wistar
4.
Braz J Med Biol Res ; 52(9): e8392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411315

RESUMO

The term inflammaging is now widely used to designate the inflammatory process of natural aging. During this process, cytokine balance is altered, presumably due to the loss of homeostasis, thus contributing to a greater predisposition to disease and exacerbation of chronic diseases. The aim of the study was to analyze the relationship between pro-inflammatory markers and age in the natural aging process of healthy individuals. One hundred and ten subjects were divided into 5 groups according to age (22 subjects/group). Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were quantified using the ELISA method. High-sensitivity C-reactive protein (hsCRP) was analyzed by turbidimetry according to laboratory procedures. The main findings of this study were: a positive correlation between hsCRP and IL-6 as a function of age (110 subjects); women showed stronger correlations; the 51-60 age group had the highest values for hsCRP and IL-6; women presented higher values for hsCRP in the 51-60 age group and higher values for IL-6 in the 61-70 age group; and men showed higher values in the 51-60 age group for hsCRP and IL-6. In conclusion, the natural aging process increased IL-6 and hsCRP levels, which is consistent with the inflammaging theory; however, women presented stronger correlations compared to men (IL-6 and hsCRP) and the 51-60 age range seems to be a key point for these increases. These findings are important because they indicate that early preventive measures may minimize the increase in these inflammatory markers in natural human aging.


Assuntos
Envelhecimento/fisiologia , Imunossenescência/fisiologia , Inflamação/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/análise , Proteína C-Reativa/análise , Colesterol/sangue , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Fatores Sexuais , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
5.
Vasc Health Risk Manag ; 15: 209-220, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371977

RESUMO

Cholesterol-embolization syndrome (CES) is a multisystemic disease with various clinical manifestations. CES is caused by embolization of cholesterol crystals (CCs) from atherosclerotic plaques located in the major arteries, and is induced mostly iatrogenically by interventional and surgical procedures; however, it may also occur spontaneously. Embolized CCs lead to both ischemic and inflammatory damage to the target organ. Therefore, anti-inflammatory agents, such as corticosteroids and cyclophosphamide, have been investigated as treatment for CES in several studies, with conflicting results. Recent research has revealed that CES is actually a kind of autoinflammatory disease in which inflammasome pathways, such as NLRP3 and IL1, are induced by CCs. These recent findings may have clinical implications such that colchicine and IL1 inhibitors, namely canakinumab, may be beneficial in the early stages of CES.


Assuntos
Aterosclerose , Colesterol/sangue , Embolia de Colesterol , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cristalização , Embolia de Colesterol/sangue , Embolia de Colesterol/diagnóstico , Embolia de Colesterol/epidemiologia , Embolia de Colesterol/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Inflamassomos/sangue , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Síndrome
6.
J Zoo Wildl Med ; 50(2): 330-336, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260197

RESUMO

Analysis of serum parameters provides information about body condition, nutritional state, and health status of individuals/species, and has broad application in ecological research and veterinary diagnosis. This study establishes baseline values for serum chemistries of the Olrog's gull (Larus atlanticus). Glucose, urea, uric acid, total protein, globulin, albumin, cholesterol, triglyceride, calcium, and phosphorus concentrations were determined, as was the activity of the following enzymes: alkaline phosphatase, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase. Thirty nonbreeding gulls (juvenile and subadult individuals) were captured and studied in Mar Chiquita Reserve (Buenos Aires, Argentina) during the wintering periods 2016 (n = 17) and 2017 (n = 13). In general terms, most values for the parameters reported were in line with those previously described for other seabirds. The year had a significant effect on several of the biochemical parameters evaluated, and the sex had a significant effect on the alkaline phosphatase and calcium. This study has defined the serum biochemical reference signatures for free-ranging Olrog's gulls during the nonbreeding period, and contributes to the knowledge of the overall health status of this threatened and endemic species.


Assuntos
Animais Selvagens , Charadriiformes/sangue , Testes Hematológicos/veterinária , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Argentina , Aspartato Aminotransferases/sangue , Glicemia , Proteínas Sanguíneas , Cálcio/sangue , Charadriiformes/fisiologia , Colesterol/sangue , Creatina Quinase/sangue , Feminino , Masculino , Fósforo/sangue , Estações do Ano , Albumina Sérica , Soroglobulinas , Triglicerídeos/sangue , Ureia/sangue , Ácido Úrico/sangue
7.
J Agric Food Chem ; 67(32): 8794-8809, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31345023

RESUMO

Oxidative stress may play a critical role in the progression of liver disorders. Increasing interest has been given to the associations among diet, oxidative stress, gut-liver axis, and nonalcoholic fatty liver disease. Here, we investigated the effects of processed meat proteins on biomarkers of lipid homeostasis, hepatic metabolism, antioxidant functions, and gut microbiota composition in glutaredoxin1 deficient (Glrx1-/-) mice. The wild-type (WT) and Glrx1-/- mice were fed a soy protein diet (SPD), a dry-cured pork protein diet (DPD), a braised pork protein diet (BPD), and a cooked pork protein diet (CPD) at a dose of 20% of protein for 3 months. Serum and hepatic total cholesterol, serum endotoxin, hepatic liver droplet %, and antioxidant capacity were significantly increased in the CPD fed WT mice. In addition, CPD fed Glrx1-/- mice significantly increased total cholesterol, triacylglycerol, and pro-inflammatory cytokines which are accompanied by higher steatosis scores, intrahepatic lipid accumulation, and altered gene expression associated with lipid metabolism. Furthermore, hepatic gene expression of Nrf2/keap1 signaling pathway and its downstream signaling targets were determined using RT-qPCR. Glrx1 deficiency increased Nrf2 activity and expression of its target genes (GPx, catalase, SOD1, G6pd, and Bbc3), which was exacerbated by intake of CPD. Metagenomic analyses revealed that Glrx1-/- mice fed meat protein diets had higher abundances of Mucispirillum, Oscillibacter, and Mollicutes but lower abundances of Bacteroidales S24-7 group_norank, Blautia, and Anaerotruncus than their wild-type counterparts. In summary, Glrx1 deficiency induced an increase in serum biomarkers for lipid homeostasis, gut microbiota imbalance, and upregulation of Nrf2/Keap1 and antioxidant defense genes, which was aggravated by cooked meat protein diet.


Assuntos
Glutarredoxinas/genética , Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipogênese , Fígado/metabolismo , Produtos da Carne/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Colesterol/sangue , Citocinas/metabolismo , Feminino , Microbioma Gastrointestinal , Glutarredoxinas/deficiência , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/microbiologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Carne Vermelha , Transdução de Sinais , Triglicerídeos/sangue
8.
Braz J Med Biol Res ; 52(7): e8429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314852

RESUMO

The present study aimed to analyze age-related changes to motor coordination, balance, spinal cord oxidative biomarkers in 3-, 6-, 18-, 24-, and 30-month-old rats. The effects of low-intensity exercise on these parameters were also analyzed in 6-, 18-, and 24-month-old rats. Body weight, blood glucose, total cholesterol, and high-density lipoprotein (HDL) cholesterol were assessed for all rats. The soleus muscle weight/body weight ratio was used to estimate skeletal muscle mass loss. Body weight increased until 24 months; only 30-month-old rats exhibited decreased blood glucose and increased total cholesterol and HDL cholesterol. The soleus muscle weight/body weight ratio increased until 18 months, followed by a small decrease in old rats. Exercise did not change any of these parameters. Stride length and step length increased from adult to middle age, but decreased at old age. Stride width increased while the sciatic functional index decreased in old rats. Performance in the balance beam test declined with age. While gait did not change, balance improved after exercise. Aging increased superoxide anion generation, hydrogen peroxide levels, total antioxidant capacity, and superoxide dismutase activity while total thiol decreased and lipid hydroperoxides did not change. Exercise did not significantly change this scenario. Thus, aging increased oxidative stress in the spinal cord, which may be associated with age-induced changes in gait and balance. Regular low-intensity exercise is a good alternative for improving age-induced changes in balance, while beneficial effects on gait and spinal cord oxidative biomarkers cannot be ruled out because of the small number of rats investigated (n=5 or 6/group).


Assuntos
Fatores Etários , Biomarcadores/sangue , Marcha/fisiologia , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal/fisiologia , Equilíbrio Postural/fisiologia , Medula Espinal/fisiologia , Animais , Biomarcadores/metabolismo , Glicemia/análise , Peso Corporal/fisiologia , Colesterol/sangue , Lipoproteínas HDL/sangue , Masculino , Ratos , Ratos Wistar , Medula Espinal/metabolismo
9.
N Engl J Med ; 381(11): 1001-1010, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340089

RESUMO

BACKGROUND: Roxadustat (FG-4592) is an oral inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase that stimulates erythropoiesis and regulates iron metabolism. In phase 2 studies involving patients with chronic kidney disease, roxadustat increased levels of endogenous erythropoietin to within or near the physiologic range, along with increasing hemoglobin levels and improving iron homeostasis. Additional data are needed regarding the efficacy and safety of roxadustat for the treatment of anemia in patients with chronic kidney disease who are not undergoing dialysis. METHODS: In this phase 3 trial conducted at 29 sites in China, we randomly assigned 154 patients with chronic kidney disease in a 2:1 ratio to receive roxadustat or placebo three times a week for 8 weeks in a double-blind manner. All the patients had a hemoglobin level of 7.0 to 10.0 g per deciliter at baseline. The randomized phase of the trial was followed by an 18-week open-label period in which all the patients received roxadustat; parenteral iron was withheld. The primary end point was the mean change from baseline in the hemoglobin level, averaged over weeks 7 through 9. RESULTS: During the primary-analysis period, the mean (±SD) change from baseline in the hemoglobin level was an increase of 1.9±1.2 g per deciliter in the roxadustat group and a decrease of 0.4±0.8 g per deciliter in the placebo group (P<0.001). The mean reduction from baseline in the hepcidin level (associated with greater iron availability) was 56.14±63.40 ng per milliliter in the roxadustat group and 15.10±48.06 ng per milliliter in the placebo group. The reduction from baseline in the total cholesterol level was 40.6 mg per deciliter in the roxadustat group and 7.7 mg per deciliter in the placebo group. Hyperkalemia and metabolic acidosis occurred more frequently in the roxadustat group than in the placebo group. The efficacy of roxadustat in hemoglobin correction and maintenance was maintained during the 18-week open-label period. CONCLUSIONS: In Chinese patients with chronic kidney disease who were not undergoing dialysis, those in the roxadustat group had a higher mean hemoglobin level than those in the placebo group after 8 weeks. During the 18-week open-label phase of the trial, roxadustat was associated with continued efficacy. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652819.).


Assuntos
Anemia/tratamento farmacológico , Glicina/análogos & derivados , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Acidose/induzido quimicamente , Adulto , Idoso , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue
10.
N Engl J Med ; 381(11): 1011-1022, 2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31340116

RESUMO

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS: In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS: A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 µg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS: Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).


Assuntos
Anemia/tratamento farmacológico , Epoetina alfa/uso terapêutico , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Hemoglobinas/análise , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Isoquinolinas/uso terapêutico , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Análise de Variância , Anemia/etiologia , Colesterol/sangue , Método Duplo-Cego , Epoetina alfa/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Humanos , Hiperpotassemia/induzido quimicamente , Hipertensão/induzido quimicamente , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia
11.
DNA Cell Biol ; 38(9): 962-968, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31361523

RESUMO

Previous studies revealed that the rs671 polymorphism in the acetaldehyde dehydrogenase 2 (ALDH2) genes is correlated with alcohol consumption in Japanese population. The ALDH2 gene variants and drinking are associated with hypertension and dyslipidemia. However, it remains unclear whether there might be potent relationships among ALDH2 rs671 polymorphism, alcohol consumption, hypertension, and dyslipidemia in Shandong population. A total of 467 male volunteers from Shandong area were enrolled in this study. The ALDH2 rs671 polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism. The concentrations of total cholesterol (TC), triglycerides, low-density lipoprotein, and high-density lipoprotein (HDL) in serum were measured using commercial kits. SPSS 23.0 was used for statistical analysis. The significance of differences between subgroups was determined using chi-square test, and multiple comparisons were performed with the least-significant difference method. The ALDH2 variant frequencies were 80.5% with GG, 17.1% with GA, and 2.4% with AA. The ALDH2 genotypes had significant correlations with alcohol consumption (p = 0.001), whereas the GA genotype was associated with a decreased risk of alcohol consumption (odds ratio = 0.27; 95% confidence interval = 0.130-0.539; p = 0.001). The ALDH2 genotypes frequencies and drinking habits were significantly different between hypertension and healthy individuals (p = 0.034; p = 0.044). The ALDH2 GG genotype individuals have high average lipids levels, and the proportion of TC disorder among GG individuals was higher than that of GA individuals (p = 0.006). Individuals who had drinking habits have a high average lipids levels; especially average TC levels (p = 0.048), and had high proportions of dyslipidemia (TC and HDL; p = 0.016 and p = 0.033, respectively). The frequencies of ALDH2 variants were evaluated according to the Hardy-Weinberg equilibrium among enrolled population. Our study suggested that the individuals with ALDH2 rs671 GA genotype were less prone to developing a drinking habit in Shandong population. The ALDH2 genotypes and drinking habit were associated with hypertension and lipid profiles especially TC profile in Shandong province. The ALDH2 rs671 genotypes indicated that the gene-related drinking habit and gene variant altogether may affect hypertension and dyslipidemia.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Colesterol/sangue , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , China , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade
12.
Life Sci ; 232: 116643, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299237

RESUMO

AIMS: Increased plasma soluble endoglin concentrations (sEng) are frequently detected in metabolic disorders accompanied with hypercholesterolemia in serum, but effect of sEng on the cholesterol biochemistry is unknown. Cholesterol and bile acids (BA) are important products of liver metabolism with numerous functions within the organism. Turnover of these substances requires precise regulation due to potential toxicities during their cumulation. In this study, we hypothesized that high sEng levels affect cholesterol homeostasis and BA turnover in mice liver. MAIN METHODS: Nine-month-old transgenic male mice overexpressing human sEng and wild-type mice underwent plasma, bile, stool, and organ samples analysis by analytical, qRT-PCT and Western blot methods. KEY FINDINGS: sEng mice demonstrated decreased plasma total and LDL cholesterol concentrations due to upregulation of hepatic Sr-b1 and Ldlr receptors, increased liver cholesterol content, and increased Abcg8-mediated cholesterol efflux into bile. sEng also increased conversion of cholesterol into bile acids (BA) via upregulation of Cyp7a1 and increased Mdr1 expression. Plasma concentrations of BA were increased in sEng mice due to their enhanced reabsorption via ileum. Increased hepatic disposition of BA led to their increased biliary excretion coupled with choleretic activity. SIGNIFICANCE: For the first time, we have shown that high sEng plasma levels affect cholesterol and BA homeostasis on the basis of complex liver and intestinal effects. The significance of these findings for pathophysiology of diseases associated with increased sEng concentrations remains to be elucidated in prospective studies.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Endoglina/sangue , Endoglina/fisiologia , Homeostase , Fígado/metabolismo , Animais , Ácidos e Sais Biliares/sangue , Colesterol/sangue , Fezes , Inflamação/sangue , Masculino , Camundongos , Camundongos Transgênicos , Transportadores de Ânions Orgânicos Dependentes de Sódio/metabolismo , Estresse Oxidativo , Receptores de LDL/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Simportadores/metabolismo , Regulação para Cima
13.
Medicine (Baltimore) ; 98(26): e16172, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261548

RESUMO

INTRODUCTION: A progressive decline in lean body mass and increase in fat mass occur with aging, and result in progressive weakness and impaired mobility; these features are altogether landmarks of the ageing frailty syndrome. High-fat mass and low muscle mass are both associated with an increased risk of cardiovascular events and are supposed to be risk factors for arterial stiffness. Little data analyzing the relationship between body composition and cardio-ankle vascular index (CAVI) are currently available. The main objective of this study was to verify whether low muscle mass and/or high fat mass could be associated with arterial stiffness measured by CAVI. METHODS: Data are from the cross-sectional assessment of the "Al passo con la tua salute", a clinical study aimed to promote physical function among free-living elderly subjects.After a screening interview and a clinical visit aimed to exclude ineligible persons, 52 volunteers were enrolled in the study. All underwent: clinical examination, physical performance assessment, an interview on lifestyle and dietary habits, and lastly, a blood sample collection after at least 8 hours of fasting. RESULTS: CAVI was statistically significantly higher in those participants in the highest tertile of distribution for fat mass compared to all other subjects (P = .03). In those participants in the lowest tertile of distribution of muscle mass, compared to all other, CAVI was also statistically significant higher (P = .01) independently of age, sex, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and systolic blood pressure. CONCLUSIONS: Low muscle mass and high fat mass were landmarks in the frailty model of aging; therefore, it is not inconsistent that both clinical conditions might share with the "aging vessel" a common pathway, probably mediated through signaling network deregulation and/or through alteration of the balance between energy availability and energy demand.


Assuntos
Tecido Adiposo , Composição Corporal , Músculo Esquelético , Rigidez Vascular , Tecido Adiposo/patologia , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Colesterol/sangue , Estudos Transversais , Dieta , Feminino , Fragilidade/epidemiologia , Fragilidade/patologia , Fragilidade/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Fatores de Risco
14.
Pan Afr Med J ; 32: 141, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308859

RESUMO

Introduction: Sickle cell anaemia (SCA) is an inherited abnormality of haemoglobin associated with reduced life expectancy. Patients' complications include dyslipideamia. This study was aimed at determining the artherogenic index of plasma (AIP) in sickle cell anaemia patients and compares the value to HbAA controls value. A high AIP is strongly predictive of elevated cardiovascular risk. Methods: A comparative study was conducted among SCA patients attending the haematology clinic, Lagos State University Teaching Hospital (LASUTH) and HbAA Phenotype controls. A total of 304 participants were recruited consisting of equal numbers of SCA and HbAA controls. Single lipid profiles were done; logarithms of triglycerides/high density lipoprotein were calculated to obtain AIP and lipid profile ratios established for all participants. Results: There were lower mean values of Total Cholesterol (TC), High Density Lipoprotein(HDL) and Low Density Lipoprotein (LDL) amongst SCD participants than controls and higher mean values of triglycerides (TG) and Very Low Density Lipoprotein (VLDL) in SCD p < 0.05. The AIP in SCD ranges from -0.62 to 1.32 while that of controls ranges from -0.56 to 0.61.The mean AIP were 0.14 ± 0.29 and -0.009 ± 0.26 in SCD and controls respectively. P value = 0.002. Conclusion: AIP value is higher in sickle cell anaemia than controls, the former have lower mean values of TC, HDL and LDL and higher mean values of TG and VLDL.


Assuntos
Anemia Falciforme/complicações , Colesterol/sangue , Dislipidemias/epidemiologia , Lipídeos/sangue , Adolescente , Adulto , Anemia Falciforme/sangue , Aterosclerose/sangue , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Hospitais Universitários , Humanos , Masculino , Nigéria , Fatores de Risco , Adulto Jovem
15.
Angiology ; 70(9): 853-859, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31167539

RESUMO

This study evaluated the prognostic value of remnant lipoprotein cholesterol (RLP-C) as a predictor of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation in patients with coronary artery disease (CAD). Consecutive patients with CAD (n = 612) who underwent both successful coronary DES implantation and follow-up angiography ranging from 6 to 24 months were enrolled. The independent predictors of ISR were explored by multivariate logistic regression analysis; 95 (15.52%) patients were identified to have ISR. Multivariate logistic regression analysis showed that RLP-C concentration (odds ratio [OR]: 4.245, 95% confidence interval [CI]: 2.493-7.229), age (OR: 1.026, 95% CI: 1.002-1.051), diabetes mellitus (DM; OR: 1.811, 95% CI: 1.134-2.892), and lesion length (OR: 1.013, 95% CI: 1.002-1.024) were associated with ISR. Via subgroup analysis, we found that RLP-C was independently associated with ISR in both CAD with DM (OR: 4.154, 95% CI: 1.895-9.104) and CAD without DM (OR: 4.455, 95% CI: 2.097-9.464) groups. In the analysis of the receiver operating characteristics curve, RLP-C level >0.515 mmol/L exhibited 77.9% sensitivity and 56.5% specificity (area under the curve: 0.705, 95% CI: 0.648-0.762) in predicting ISR. In conclusion, RLP-C is independently associated with the development of ISR in patients with CAD after DES implantation.


Assuntos
Colesterol/sangue , Doença da Artéria Coronariana/etiologia , Reestenose Coronária/sangue , Stents Farmacológicos/efeitos adversos , Lipoproteínas/sangue , Idoso , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Diabetes Mellitus/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC
16.
Eur J Med Chem ; 178: 108-115, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176093

RESUMO

As dual regulators, the PTP-1B signaling pathway and α-glucosidase slow glucose release and increase the degree of insulin sensitivity, representing a promising therapeutic target for type 2 diabetes. In this study, we systematically examined the in vivo and in vitro anti-diabetic activities of natural flavonoids 1-6 from Chrysanthemum morifolium. Flavonoids 1-6 increased glucose consumption-promoting activity and the phosphorylation of GSK-3ß and Akt, and decreased PTP-1B protein level along with slightly inhibitory activity of the PTP-1B enzyme. Moreover, flavonoids 1-2 treatment induced insulin secretion in INS-1 cells. Besides, in vivo study revealed that flavonoids 2 and 5 demonstrated potent anti-hyperglycemic and anti-hyperlipidemic activity, and improved maltose and glucose tolerance. Although flavonoid 2 exhibited lower inhibitory activity against α-glucosidase in vitro, it could deglycosylated in vivo to diosmetin to function as an α-glucosidase inhibitor. Taken together, these results led to the identification of the natural flavonoids 1-6 from C. morifolium as dual regulators of α-glucosidase and the PTP-1B signaling pathway, suggesting their potential application as new oral anti-diabetic drugs or functional food ingredients.


Assuntos
Chrysanthemum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/uso terapêutico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Colesterol/sangue , Cricetulus , Diabetes Mellitus Experimental/induzido quimicamente , Flavonoides/isolamento & purificação , Glucose/metabolismo , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Masculino , Camundongos , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Ratos , Estreptozocina , Triglicerídeos/sangue
17.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172973

RESUMO

Obesity is characterised by imbalance in lipid metabolism manifested by high concentrations of circulating triacylglycerols and total cholesterol as well as low high-density lipoprotein (HDL) levels. Abnormalities related to these lipids lead to metabolic complications such as type 2 diabetes, arterial hypertension and cardiovascular disease. Despite extensive research, it is still unclear why a subset of obese subjects develop metabolic syndrome, while others do not. The aim of our work was to assess total and plasma membrane expressions of cholesterol transport proteins: adipocyte ATP-binding cassette A1 (ABCA1), adipocyte ATP-binding cassette G1 (ABCG1), class B scavenger receptor (SR-BI) in visceral and subcutaneous adipose tissue of obese subjects with and without metabolic syndrome. To keep our preliminary study group uniform, we focused on women, who constitute the majority of bariatric patients. The study was performed on 34 patients: 24 morbidly obese women subjected to bariatric surgery, half of whom had metabolic syndrome; and 10 lean subjects undergoing elective laparoscopic cholecystectomy. Total and plasma membrane expressions of cholesterol transport proteins (SR-BI, ABCA1 and ABCG1) were assessed in samples of both visceral and subcutaneous adipose and analysed in relation to other clinical and laboratory parameters. We demonstrated lower plasma membrane expressions of ABCG1 in visceral adipose tissue of obese patients with metabolic syndrome as compared to lean ones. In addition, total ABCG1 expressions in both types of adipose tissue were lower in morbidly obese patients with metabolic syndrome compared to those without metabolic syndrome. Plasma membrane ABCA1 expressions in visceral adipose tissue were lower in the group of morbidly obese patients without metabolic syndrome, compared to lean patients. We did not find any significant differences in SR-BI expressions. Because of ABCG1 is responsible for cholesterol efflux to HDL, reduced plasma membrane expression of ABCG1 in VAT of morbidly obese women with metabolic syndrome may leads to a significantly decreased concentration of HDL in serum. This may be also confirmed by high positive correlation between both parameters.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Tecido Adiposo/metabolismo , Síndrome Metabólica/metabolismo , Obesidade Mórbida/metabolismo , Adulto , Idoso , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Pessoa de Meia-Idade , Receptores Depuradores Classe B/metabolismo , Adulto Jovem
18.
Einstein (Sao Paulo) ; 17(3): eAO4399, 2019 May 30.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31166482

RESUMO

OBJECTIVE: To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay. METHODS: Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study. RESULTS: Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease. CONCLUSION: Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.


Assuntos
Lesão Renal Aguda/terapia , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/efeitos dos fármacos , Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Terapia de Substituição Renal/estatística & dados numéricos , Triglicerídeos , APACHE , Lesão Renal Aguda/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Creatinina/sangue , Cuidados Críticos/métodos , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Valores de Referência , Terapia de Substituição Renal/mortalidade , Reprodutibilidade dos Testes , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangue , Adulto Jovem
19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(5): 542-547, 2019 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-31177735

RESUMO

Objective: To analyze the longitudinal change of serum total cholesterol concentration in 733 rural residents in Shanxi province. Methods: Based on the residents of five rural areas in Shanxi province who participated in China nutrition and health survey in 2002, a follow-up survey was conducted in 2015. Fasting venous blood of the participants was collected and serum TC concentration was tested by cholesterol oxidase method. Results: Of 733 participants, 332 were male and 401 were female. In 2002 baseline survey, the age of the participants was (42.6±9.5) years old, 76.2% of male and 83.8% of female had junior middle school education or below. Proportion of smoking were 65.7% and 1.2%, drinking were 26.8% and 4.0%, obesity were 6.3% and 12.0%, and central obesity were 27.1% and 31.9%, respectively in male and female. The follow-up age of participants in 2015 was (55.8±9.5) years old, proportion of smoking changed to 48.2% and 1.5%, drinking were 49.7% and 3.0%, obesity increased to 11.8% and 18.2% and central obesity increased to 41.6% and 53.6%, respectively in male and female. The overall serum TC level increased from (3.82±0.89) mmol/L to (4.72±0.97) mmol/L with an average increase of 27.2%, which increased from (3.84±0.94) mmol/L to (4.54±0.93) mmol/L in male with an average increase of 22.7%, and increased from (3.81±0.84) mmol/L to (4.86±0.98) mmol/L in female with an average increase of 30.9%. The serum TC levels in 18-, 30-, 40-, and 50-59 years old group increased from (3.42±0.83), (3.72±0.77), (3.90±0.83) and (4.00±1.03) mmol/L to (4.38±1.01), (4.79±0.92), (4.73±0.99) and (4.76±0.96) mmol/L, with average increase range of 31.4%, 32.1%, 25.2% and 22.6%, respectively. The mean serum TC levels between two years all had statistically significant difference among groups of gender, age, education, marital status, family history of cardiovascular disease, smoking, drinking, BMI and waist circumference after paired t-test and ANOVA analysis (P<0.01). Conclusion: The longitudinal serum TC level of rural residents in Shanxi province increased rapidly.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Colesterol/sangue , Hipercolesterolemia/epidemiologia , População Rural , Adulto , Idoso , China/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade
20.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31152112

RESUMO

Cholesterol efflux capacity (CEC), an important functional step in reverse cholesterol transport, is the main anti-atherosclerotic function of high-density lipoprotein (HDL). Assays that improve the determination of CEC ex vivo for clinical applications are constantly explored. In the accompanying article, Horiuchi et al. (Biosci. Rep. (2019) 39(4), BSR20190213) evaluate the availability of apolipoprotein B-depleted serum for CEC assays. Using their recently developed immobilized liposome-bound gel beads (ILG) method, Horiuchi et al. demonstrate that apolipoprotein B-depleted serum obtained with poly ethylene glycol precipitation enables CEC assays to be easily and accurately introduced into laboratory medicine.


Assuntos
Colesterol/sangue , Lipossomos , Apolipoproteínas B/sangue , Transporte Biológico , Lipoproteínas HDL/sangue
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