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1.
BMJ ; 371: m3109, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046451

RESUMO

Hypertriglyceridemia is one of the most common lipid abnormalities encountered in clinical practice. Many monogenic disorders causing severe hypertriglyceridemia have been identified, but in most patients triglyceride elevations result from a combination of multiple genetic variations with small effects and environmental factors. Common secondary causes include obesity, uncontrolled diabetes, alcohol misuse, and various commonly used drugs. Correcting these factors and optimizing lifestyle choices, including dietary modification, is important before starting drug treatment. The goal of drug treatment is to reduce the risk of pancreatitis in patients with severe hypertriglyceridemia and cardiovascular disease in those with moderate hypertriglyceridemia. This review discusses the various genetic and acquired causes of hypertriglyceridemia, as well as current management strategies. Evidence supporting the different drug and non-drug approaches to treating hypertriglyceridemia is examined, and an easy to adopt step-by-step management strategy is presented.


Assuntos
Gerenciamento Clínico , Hipertrigliceridemia/terapia , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/genética , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Pancreatite/etiologia , Pancreatite/prevenção & controle , Fatores de Risco , Triglicerídeos/sangue
2.
Medicine (Baltimore) ; 99(35): e21574, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871873

RESUMO

The prevalence of the metabolic syndrome (MS) is increasing in China, but there are disparities between urban and rural populations, and across different regions.To examine the prevalence and risk factors of MS in the rural area of Qianjiang (Southwest China).From March 2016 to June 2018, 6 townships in the Qianjiang District of Chongqing Municipality were selected for a cross-sectional study of the residents in rural areas. Demographics and medical history were collected using a questionnaire. Anthropometry and blood pressure were obtained by physical examination. Blood lipids, fasting plasma glucose, and 2-h postprandial glucose were measured.A total of 2949 (1067 males and 1882 females) were included. The mean age was 63.8 ±â€Š10.7 years. The prevalence of MS in the study population was 16.8% (496/2949). The prevalence of MS was 7.4% in men, 22.2% in women, 15.7% in Han, 18.1% in Tujia, and 14.8% in Miao. According to age, the prevalence of MS was 10.6%, 17.0%, and 18.3% in the 30-50, 50-69, and ≥ 70 years groups. The multivariable analysis showed that female sex (OR = 33.36, 95%CI: 17.0-65.53), dyslipidemia (OR = 4.71, 95%CI: 1.73-12.82), kidney diseases (OR = 2.32, 95%CI: 1.37-3.94), waistline (OR = 1.39, 95%CI: 1.33-1.46), high-density lipoprotein cholesterol (OR = 0.12, 95%CI: 0.06-0.23), triglycerides (OR = 1.52, 95%CI: 1.31-1.76), alanine aminotransferase (OR = 0.98, 95%CI: 0.97-1.00), γ-glutamyltransferase (OR = 1.00, 95%CI: 1.00-1.01), and glycated hemoglobin (OR = 1.31, 95%CI: 1.08-1.59) were independently associated with MS.The prevalence of MS was 16.8% in Qianjiang. Female sex, kidney diseases, alanine aminotransferase, and γ-glutamyltransferase were independent risk factors for MS.


Assuntos
Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , População Rural/tendências , Idoso , Alanina Transaminase/sangue , Antropometria , Glicemia/análise , Pressão Sanguínea/fisiologia , China/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/epidemiologia , Jejum/sangue , Feminino , Humanos , Nefropatias/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Triglicerídeos/sangue , gama-Glutamiltransferase/sangue
3.
Medicine (Baltimore) ; 99(35): e21654, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871878

RESUMO

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Vitamina D/análogos & derivados , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China , Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Gravidez , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue
4.
Lipids Health Dis ; 19(1): 204, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892746

RESUMO

BACKGROUND: The purpose of the study is to describe the blood lipid levels of patients diagnosed with coronavirus disease 2019 (COVID-19) and to analyze the correlation between blood lipid levels and the prognosis of COVID-19 patients. METHODS: In the clinical retrospective analysis, a total of 228 adults infected with COVID-19 were enrolled between January 17, 2020 and March 14, 2020, in Changsha, China. One thousand one hundred and forty healthy participants with matched age and gender were used as control. Median with interquartile range and Mann-Whitney test were adopted to describe and analyze clinical data. The Kaplan-Meier (KM) curve and Cox regression analysis were used to analyze the correlation between high-density lipoprotein cholesterol (HDL-C) and the severity of COVID-19. RESULTS: Compared with control, COVID-19 patients showed significantly lower levels of total cholesterol (TC) [median, 3.76 vs 4.65 mmol/L, P = 0.031], triglyceride [median, 1.08 vs 1.21 mmol/L, P <  0.001], low-density lipoprotein cholesterol (LDL-C) [median, 2.63 vs 2.83 mmol/L, P <  0.001], and HDL-C [median, 0.78 vs 1.37 mmol/L, P <  0.001], while compared with non-severe patients, severe COVID-19 patients only presented lower levels of HDL-C [median, 0.69 vs 0.79 mmol/L, P = 0.032]. In comparison with patients with high HDL-C, patients with low HDL-C showed a higher proportion of male (69.57% vs 45.60%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P <  0.001) and higher proportion of severe events (36.96% vs 14.84%, P = 0.001). Moreover, patients with low HDL-C at admission showed a higher risk of developing severe events compared with those with high HDL-C (Log Rank P = 0.009). After adjusting for age, gender and underlying diseases, they still had elevated possibility of developing severe cases than those with high HDL-C (HR 2.827, 95% CI 1.190-6.714, P = 0.019). CONCLUSIONS: HDL-C level was lower in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.


Assuntos
Betacoronavirus , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Adulto , Proteína C-Reativa/análise , China , Colesterol/sangue , Infecções por Coronavirus/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Triglicerídeos/sangue
5.
Diab Vasc Dis Res ; 17(5): 1479164120952321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32883101

RESUMO

BACKGROUND: Estimated glucose disposal rate (eGDR) is a practical measure of Insulin Resistance (IR) which can be easily incorporated into clinical practice. We profiled eGDR in younger adults with type 1 diabetes mellitus (T1DM) by their demographic and clinical characteristics. METHODS: In this single centre study, medical records of TIDM were assessed and eGDR tertiles correlated with demographic and clinical variables. RESULTS: Of 175 T1DM individuals, 108 (61.7%) were males. Mean age (±SD) was 22.0 ± 1.6 years and median time from diagnosis 11.0 years (range 1-23). Individuals were predominantly Caucasian (81.7%), with 27.4% being overweight (BMI: 25-30 kg/m2) and 13.7% obese (BMI > 30 kg/m2). Mean total cholesterol (TC) levels were significantly lower in high and middle eGDR tertiles (4.4 ± 1 and 4.3 ± 0.8 mmol/l, respectively) compared with low eGDR tertile (4.8 ± 1, p < 0.05 for both). Triglyceride (TG) levels showed a similar trend at 1.1 ± 0.5 and 1.1 ± 0.5 mmol/l for high and middle eGDR tertile compared to low eGDR tertile (1.5 ± 1 mmol/l, p < 0.05 for both). Renal function was similar across eGDR tertiles and no difference in retinopathy was detected. CONCLUSION: TC and TG are altered in individuals with T1DM and low eGDR, suggesting that this subgroup requires optimal lipid management to ameliorate their vascular risk.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Resistência à Insulina , Fatores Etários , Biomarcadores/sangue , Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Retrospectivos , Fatores de Tempo , Triglicerídeos/sangue , Adulto Jovem
6.
Medicine (Baltimore) ; 99(36): e21792, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899007

RESUMO

Major lipids making effects on the occurrence of acute ischemic stroke (AIS) is well recognized, but their roles on stroke severity remain uncertain. To explore the exact roles of lipids playing on stroke severity and the possible mechanism, we conduct this observational study.Data was collected from patients with AIS from February 2008 to May 2012. The level of major lipids was compared among AIS groups with different severity and investigated the correlation. Also, the relationship existed between major lipids and bilirubin. Mechanism of major lipids playing on stroke severity was researched to determine if oxidative stress reflected by bilirubin.Lower triglyceride (TG) and higher high density lipoprotein cholesterol (HDL-C) were observed in severe stroke, and obvious correlation existed between TG and stroke severity or HDL-C and stroke severity. TG was associated negatively with direct bilirubin (DBIL) and total bilirubin (TBIL), and lower level of DBIL and TBIL were related to higher quartiles of TG. There was no obvious difference of DBIL and TBIL among the groups of quartiles of HDL-C. TG was the influence factor of stroke severity in severe stroke through multiple univariable logistic regression. But it was not the independent influence factor after multivariable logistic regression adjusted by DBIL or TBIL. However, HDL-C was the influence factor of stroke severity through both univariable and multivariable logistic regression.Lower TG or higher HDL-C predicted severer stroke. The effect of TG on stroke severity was mediated by bilirubin, not HDL-C.


Assuntos
Bilirrubina/sangue , HDL-Colesterol/sangue , Acidente Vascular Cerebral/sangue , Triglicerídeos/sangue , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Estresse Oxidativo , Índice de Gravidade de Doença
7.
PLoS Med ; 17(9): e1003302, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32915777

RESUMO

BACKGROUND: A number of epidemiological and genetic studies have attempted to determine whether levels of circulating lipids are associated with risks of various cancers, including breast cancer (BC). However, it remains unclear whether a causal relationship exists between lipids and BC. If alteration of lipid levels also reduced risk of BC, this could present a target for disease prevention. This study aimed to assess a potential causal relationship between genetic variants associated with plasma lipid traits (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides, TGs) with risk for BC using Mendelian randomization (MR). METHODS AND FINDINGS: Data from genome-wide association studies in up to 215,551 participants from the Million Veteran Program (MVP) were used to construct genetic instruments for plasma lipid traits. The effect of these instruments on BC risk was evaluated using genetic data from the BCAC (Breast Cancer Association Consortium) based on 122,977 BC cases and 105,974 controls. Using MR, we observed that a 1-standard-deviation genetically determined increase in HDL levels is associated with an increased risk for all BCs (HDL: OR [odds ratio] = 1.08, 95% confidence interval [CI] = 1.04-1.13, P < 0.001). Multivariable MR analysis, which adjusted for the effects of LDL, TGs, body mass index (BMI), and age at menarche, corroborated this observation for HDL (OR = 1.06, 95% CI = 1.03-1.10, P = 4.9 × 10-4) and also found a relationship between LDL and BC risk (OR = 1.03, 95% CI = 1.01-1.07, P = 0.02). We did not observe a difference in these relationships when stratified by breast tumor estrogen receptor (ER) status. We repeated this analysis using genetic variants independent of the leading association at core HDL pathway genes and found that these variants were also associated with risk for BCs (OR = 1.11, 95% CI = 1.06-1.16, P = 1.5 × 10-6), including locus-specific associations at ABCA1 (ATP Binding Cassette Subfamily A Member 1), APOE-APOC1-APOC4-APOC2 (Apolipoproteins E, C1, C4, and C2), and CETP (Cholesteryl Ester Transfer Protein). In addition, we found evidence that genetic variation at the ABO locus is associated with both lipid levels and BC. Through multiple statistical approaches, we minimized and tested for the confounding effects of pleiotropy and population stratification on our analysis; however, the possible existence of residual pleiotropy and stratification remains a limitation of this study. CONCLUSIONS: We observed that genetically elevated plasma HDL and LDL levels appear to be associated with increased BC risk. Future studies are required to understand the mechanism underlying this putative causal relationship, with the goal of developing potential therapeutic strategies aimed at altering the cholesterol-mediated effect on BC risk.


Assuntos
Neoplasias da Mama/genética , Lipídeos/análise , Lipídeos/sangue , Adulto , Neoplasias da Mama/metabolismo , Colesterol/análise , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Análise da Randomização Mendeliana/métodos , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Triglicerídeos/sangue
8.
Nat Commun ; 11(1): 4611, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929072

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/metabolismo , Interleucinas/antagonistas & inibidores , Modelos Biológicos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Linfócitos T CD8-Positivos/metabolismo , Caquexia , Carcinoma Pulmonar de Lewis/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interleucinas/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/imunologia , Análise de Sobrevida , Resultado do Tratamento , Triglicerídeos/sangue , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Medicine (Baltimore) ; 99(33): e21647, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872028

RESUMO

Prevalence of postpartum depression (PD) in Chinese women is rising and its associated factors are not well known. In this study we aim to explore the associations between nutritional factors in pregnancy and the risk of PD in Chinese women.A case-control study was performed in our hospital during January 2016 to June 2019. A food frequency questionnaire was designed to collect food consumption before the childbirth preceding month. Nutrition related biochemical indicators including fasting blood-glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), and uric acid in the third trimester of pregnancy were detected. Logistic regression model was applied to compute odds ratio (OR) and its corresponding 95% confidence interval (CI).There were 565 participants in this study, which comprised 182 individuals with PD and 383 individuals without. Patients with PD had higher odds of increased GLU (OR=2.62, 95%CI = 1.67-4.11), TC (OR = 1.73 95%CI = 1.22-2.46), TG (OR = 2.43, 95%CI = 1.55-3.81), and LDL (OR = 3.41, 95%CI = 2.09-5.57), but decreased HDL (OR = 3.41, 95%CI = 2.09-5.57) during pregnancy. With respect to uric acid, there was lack of no statistical association (OR = 2.23, 95%CI = 0.82-6.26). Food frequency questionnaire indicated a higher meat intake, but a lower vegetable, fruit, fish, and poultry intake in patients with PD during pregnancy.Increased GLU, TC, TG, and LDL, but decreased HDL in later stages of pregnancy might be associated with PD.


Assuntos
Depressão Pós-Parto/etiologia , Avaliação Nutricional , Adulto , Biomarcadores/sangue , Glicemia/análise , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Gravidez , Terceiro Trimestre da Gravidez , Fatores de Risco , Triglicerídeos/sangue
10.
PLoS One ; 15(8): e0237983, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822397

RESUMO

OBJECTIVES: Although smoking is known to have a negative impact in patients with metabolic syndrome (MetS), only a few studies have examined the association between electronic cigarette (e-cig) use and MetS. METHODS: Among 22,948 participants in the 6th Korea National Health and Nutrition Examination Survey, 14,738 (13,459 [91.3%] never, 954 [6.5%] ever, and 325 [2.2%] current e-cig users) were selected. The relationship between e-cig exposure and MetS (based on the National Cholesterol Education Program Adult Treatment Panel [NCEP-ATP] III criteria) was evaluated using a multivariable logistic regression analysis. An unweighted analysis was performed to evaluate this association without a sampling weight. A subgroup analysis was performed among active smokers to compare dual users with never e-cig users. RESULTS: Among current e-cig users, 85.0% were dual users, 12.7% were former cigarette users, and 2.2% were only e-cig users. After adjustment for covariates, abdominal obesity and hypertriglyceridemia were significantly associated with current e-cig exposure (odds ratio [OR]: 1.88, 95% confidence interval [CI]: 1.41-2.50 and OR: 1.32, 95% CI: 1.00-1.74 respectively [compared with the never e-cig users group]). Compared with never e-cig users, current e-cig users showed an OR of 1.27 (95% CI: 0.96-1.70, Ptrend = 0.01) for MetS. In the unweighted analysis, the OR for MetS in current e-cig users was 1.40 (95% CI: 1.08-1.81, Ptrend <0.01). Compared with never e-cig users, dual users showed a higher OR for abdominal obesity (OR: 1.71, 95% CI: 1.25-2.34, Ptrend <0.001). CONCLUSIONS: Current e-cig exposure was associated with an increased risk of MetS. Dual use of e-cigs and cigarettes was associated with abdominal obesity. Further longitudinal studies and better assessment of e-cig use and type are needed to clarify this relationship.


Assuntos
Síndrome Metabólica/patologia , Vaping , Adulto , HDL-Colesterol/sangue , Fumar Cigarros , Feminino , Humanos , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/patologia , Modelos Logísticos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/epidemiologia , Obesidade/patologia , Razão de Chances , República da Coreia/epidemiologia , Triglicerídeos/sangue
11.
PLoS One ; 15(8): e0237148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745152

RESUMO

The susceptibility to cardiovascular disease in offspring could be reduced prior to birth through maternal intervention, before and during pregnancy. We evaluated whether the initiation periods of maternal exercise in preconception and pregnancy periods induce beneficial effects in the adult male offspring. Thirty-two female rats were divided into control and exercise groups. The exercise groups involve exercise before pregnancy or the preconception periods, exercise during pregnancy, and exercise before and during pregnancy. The mothers in the exercise groups were run on the treadmill in different periods. Then the birth weight and weekly weight gain of male offspring were measured, and the blood and left ventricle tissue of samples were collected for analysis of the Sirtuin 6 (Sirt6) and insulin growth factor-2 (IGF-2) gene expression, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (Cho), and triglycerides (TG). There was no significant difference in the birth weight of offspring groups (P = 0.246) while maternal HIIT only during pregnancy leads to reduce weekly weight gain of offspring. Our data showed that Sirt6 and IGF-2 gene expression was increased (P = 0.017) and decreased (P = 0.047) by maternal exercise prior to and during pregnancy, respectively. Also, the serum level of LDL (p = 0.002) and Cho (P = 0.007) were significantly decreased and maternal exercise leads to improves the running speed of the adult male offspring (p = 0.0176). This study suggests that maternal HIIT prior to and during pregnancy have positive intergenerational consequence in the health and physical readiness of offspring.


Assuntos
Metabolismo dos Lipídeos , Miocárdio/metabolismo , Condicionamento Físico Animal/métodos , Sirtuínas/genética , Animais , Peso ao Nascer , Doenças Cardiovasculares/prevenção & controle , Colesterol/sangue , Feminino , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Lipoproteínas LDL/sangue , Masculino , Gravidez , Ratos , Ratos Wistar , Sirtuínas/metabolismo , Triglicerídeos/sangue
12.
Arterioscler Thromb Vasc Biol ; 40(9): 2095-2107, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32757647

RESUMO

OBJECTIVE: Apo (apolipoprotein) CIII mediates the metabolism of triglyceride (TG)-rich lipoproteins. High levels of plasma apoCIII are positively correlated with the plasma TG levels and increase the cardiovascular risk. However, whether apoCIII is directly involved in the development of atherosclerosis has not been fully elucidated. Approach and Results: To examine the possible roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated apoCIII KO (knockout) rabbits using ZFN (zinc finger nuclease) technique. On a normal standard diet, apoCIII KO rabbits exhibited significantly lower plasma levels of TG than those of WT (wild type) rabbits while total cholesterol and HDL (high-density lipoprotein) cholesterol levels were unchanged. Analysis of lipoproteins isolated by sequential ultracentrifugation revealed that reduced plasma TG levels in KO rabbits were accompanied by prominent reduction of VLDLs (very-low-density lipoproteins) and IDLs (intermediate-density lipoproteins). In addition, KO rabbits showed faster TG clearance rate after intravenous fat load than WT rabbits. On a cholesterol-rich diet, KO rabbits exhibited constantly and significantly lower levels of plasma total cholesterol and TG than WT rabbits, which was caused by a remarkable reduction of ß-VLDLs-the major atherogenic lipoproteins. ß-VLDLs of KO rabbits showed higher uptake by cultured hepatocytes and were cleared faster from the circulation than ß-VLDLs isolated from WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. CONCLUSIONS: These results indicate that apoCIII deficiency facilitates TG-rich lipoprotein catabolism, and therapeutic inhibition of apoCIII expression may become a novel means not only for the treatment of hyperlipidemia but also for atherosclerosis.


Assuntos
Doenças da Aorta/prevenção & controle , Apolipoproteína C-III/deficiência , Aterosclerose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Triglicerídeos/sangue , Animais , Animais Geneticamente Modificados , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Apolipoproteína C-III/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/sangue , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Lipoproteínas IDL/sangue , Fígado/metabolismo , Masculino , Oxirredução , Placa Aterosclerótica , Coelhos
13.
BMC Infect Dis ; 20(1): 473, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620082

RESUMO

BACKGROUND: People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. METHODS: In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. RESULTS: At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV. CONCLUSION: Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.


Assuntos
Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , HIV , Síndrome de Imunodeficiência Adquirida/sangue , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Adulto , Antirretrovirais/uso terapêutico , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , HDL-Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/análise , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doenças não Transmissíveis , Análise de Onda de Pulso , Fatores de Risco , África do Sul/epidemiologia , Triglicerídeos/sangue
14.
Life Sci ; 257: 118125, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702444

RESUMO

AIM: Nonalcoholic fatty liver disease (NAFLD) is a growing health problem worldwide. Impaired autophagy has been linked to NAFLD pathogenesis. Whether transfer RNA (tRNA)-derived fragments (tRFs) regulate the progression of NAFLD via autophagy is not clear. Here, we aimed to identify autophagy- or adipogenesis-related tRFs and investigate their roles in NAFLD. METHODS: Small RNA sequencing was performed on NAFLD and control mice, and candidate tRFs were validated using quantitative reverse transcription PCR (qRT-PCR). The role of a key tRF was investigated using Oil red O staining, western blotting, qRT-PCR and a luciferase reporter assay. KEY FINDINGS: In NAFLD mice, the expression of p62 was increased and the ratio of LC3B-II/LC3-I was decreased compared to control mice. We identified nine differentially expressed tRFs, among which tRF-3001b was found to be significantly upregulated in NAFLD mice compared to the control liver tissues. Autophagy was decreased in FA (fatty acids)-induced LO2 cells, while silencing of tRF-3001b significantly abrogated the decrease in autophagy and increase in lipid formation. Moreover, chloroquine (CQ) dramatically abrogated the effect of tRF-3001b inhibition on lipid formation. Mechanistically, tRF-3001b targeted and inhibited the expression of the autophagy-related gene Prkaa1. In vivo, tRF-3001b silencing significantly improved pathology and decreased the levels of triglycerides and cholesterol in NAFLD mice, while CQ dramatically abrogated the effect of tRF-3001b deficiency. SIGNIFICANCE: tRF-3001b may aggravate the development of NAFLD by inhibiting autophagy via targeting Prkaa1.


Assuntos
Autofagia , Hepatopatia Gordurosa não Alcoólica/metabolismo , RNA de Transferência/metabolismo , Animais , Western Blotting , Linhagem Celular , Colesterol/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , RNA de Transferência/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNA , Triglicerídeos/sangue
15.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R211-R222, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609532

RESUMO

Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.3 yr, 31.7 ± 3.5 kg/m2) were randomized into three 8-wk interventions (three 1-h sessions per week): sustained hypoxia (SH), arterial oxygen saturation ([Formula: see text]) = 75%; IH, 5 min [Formula: see text] = 75% - 3 min normoxia; normoxia. Ventilation, heart rate, blood pressure, and tissue oxygenation were measured during the first and last hypoxic conditioning sessions. Vascular function, blood glucose and insulin, lipid profile, nitric oxide metabolites, and oxidative stress were evaluated before and after the interventions. Both SH and IH increased ventilation in hypoxia (+1.8 ± 2.1 and +2.3 ± 3.6 L/min, respectively; P < 0.05) and reduced normoxic diastolic blood pressure (-12 ± 15 and -13 ± 10 mmHg, respectively; P < 0.05), whereas changes in normoxic systolic blood pressure were not significant (+3 ± 9 and -6 ± 13 mmHg, respectively; P > 0.05). IH only reduced heart rate variability (e.g., root-mean-square difference of successive normal R-R intervals in normoxia -21 ± 35%; P < 0.05). Both SH and IH induced no significant change in body mass index, vascular function, blood glucose, insulin and lipid profile, nitric oxide metabolites, or oxidative stress, except for an increase in superoxide dismutase activity following SH. This study indicates that passive hypoxic conditioning in obese individuals induces some positive cardiovascular and respiratory improvements despite no change in anthropometric data and even a reduction in heart rate variability during IH exposure.


Assuntos
Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/fisiopatologia , Frequência Cardíaca/fisiologia , Hipóxia/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Sistema Cardiovascular/metabolismo , Colesterol/sangue , Feminino , Humanos , Hipóxia/metabolismo , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Método Simples-Cego , Triglicerídeos/sangue
16.
Chemosphere ; 260: 127506, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32673867

RESUMO

Ubiquitous exposure to the neonicotinoid insecticide nitenpyram has raised concerns about its potential toxicity. In this study, we explored its health effects on the female offspring of mice that had been exposed during pregnancy. We found that exposure of pregnant mice to nitenpyram resulted in decreased levels of serum triglycerides, total cholesterol, and glucose in female offspring, and additional research uncovered gut microbiota disturbances, accompanied by abnormal fecal metabolic profiles. Based on Pearson correlation analysis, we found that decreased abundance of Lactobacillus may play the most critical role, and changes in gut bacterial purine metabolism, BCAAs metabolism, and the TCA cycle are all closely related to the abundance of Lactobacillus. In summary, these results help explain the observed serum biochemical abnormalities and provide new insights into the intergenerational toxicity of nitenpyram.


Assuntos
Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Inseticidas/toxicidade , Metaboloma/efeitos dos fármacos , Neonicotinoides/toxicidade , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Animais , Bactérias , Glicemia/análise , Colesterol/sangue , Fezes/microbiologia , Feminino , Lactobacillus/efeitos dos fármacos , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Triglicerídeos/sangue
17.
Eur J Vasc Endovasc Surg ; 60(3): 452-460, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32703634

RESUMO

OBJECTIVE: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. METHODS: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. RESULTS: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. CONCLUSION: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.


Assuntos
Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/terapia , Fenofibrato/administração & dosagem , Procedimentos Cirúrgicos Vasculares , Idoso , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/patologia , Biomarcadores/sangue , Progressão da Doença , Método Duplo-Cego , Esquema de Medicação , Feminino , Fenofibrato/efeitos adversos , Humanos , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Osteopontina/sangue , Queensland , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Remodelação Vascular/efeitos dos fármacos , Procedimentos Cirúrgicos Vasculares/efeitos adversos
18.
PLoS One ; 15(7): e0236189, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697795

RESUMO

Research based on secondary analysis of data stored in electronic health records (EHR) has gained popularity, but whether the data are consistent with those collected under a study setting is unknown. The objective is to assess the agreement between data obtained in a prospective study and routine-care data extracted retrospectively from the EHR. We compared the data collected in a longitudinal lifestyle intervention study with those recorded in the EHR system over 5 years. A total of 225 working adults were recruited at an academic institution between 2008-2012, whose EHR data were also available during the same time period. After aligning the participants' study visit dates with their hospital encounter dates, data on blood pressure, body mass index (BMI), and laboratory measurements (including high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol) were compared via a paired t-test for equivalence with pre-specified margins. Summary statistics were used to compare smoking status and medication prescriptions. Overall, data were consistent between the two sources (i.e., BMI, smoking status, medication prescriptions), whereas some differences were found in cholesterol measurements (i.e., HDL and total cholesterol), possibly due to different lab assays and subject's fasting status. In conclusion, some EHR data are fairly consistent with those collected in a clinical study, whereas others may require further examination. Researchers should evaluate the consistency and quality of EHR data and compare them with other sources of data when possible.


Assuntos
Coleta de Dados/métodos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Comportamento de Redução do Risco , Adulto , Idoso , Determinação da Pressão Arterial/estatística & dados numéricos , Índice de Massa Corporal , Colesterol/sangue , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fumar/efeitos adversos , Fumar/epidemiologia , Triglicerídeos/sangue , Adulto Jovem
19.
Intern Med ; 59(14): 1705-1710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32669515

RESUMO

Objective Lipoprotein (a), or Lp (a), has been shown to be associated with the development of chronic kidney disease (CKD) in populations of various ethnicities. This study aimed to investigate the association between serum Lp (a) and CKD in Japanese patients. Methods A total of 6,130 subjects who underwent a serum Lp (a) level assessment for any reason (e.g. any type of surgery requiring prolonged bed rest or risk factors for atherosclerosis, such as hypertension or diabetes) were retrospectively investigated at Kanazawa University Hospital from April 2004 to March 2014. Of these, 1,895 subjects were excluded because of the lack of clinical data. Subjects were assessed for Lp (a), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hypertension, diabetes, smoking, body mass index (BMI), coronary artery disease (CAD), and CKD (stage ≥3). Results When the study subjects were divided into quartiles of Lp (a) levels, significant trends were observed with regard to the presence of CKD (p = 2.7×10-13). A multiple regression analysis showed that Lp (a) was significantly associated with CKD [odds ratio (OR), 1.12; 95% confidence interval (CI), 1.08-1.17; p = 1.3×10-7, per 10 mg/dL], independent of other classical risk factors, including age, gender, BMI, hypertension, diabetes, smoking, LDL cholesterol, and triglycerides. Under these conditions, Lp (a) was significantly associated with CAD (OR = 1.11, 95% CI = 1.06-1.16; p = 1.7×10-6, per 10 mg/dL), independent of other risk factors. Conclusion Serum Lp (a) was associated with CKD, independent of other classical risk factors in a Japanese population.


Assuntos
Hiperlipidemias/complicações , Lipoproteína(a)/sangue , Insuficiência Renal Crônica/etiologia , Adulto , Idoso , Doenças Cardiovasculares/complicações , LDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos/sangue
20.
PLoS One ; 15(7): e0235990, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32701948

RESUMO

BACKGROUND AND AIMS: Alcoholic steatohepatitis (ASH)-the inflammation of fatty liver-is caused by chronic alcohol consumption and represents one of the leading chronic liver diseases in Western Countries. ASH can lead to organ dysfunction or progress to hepatocellular carcinoma (HCC). Long-term alcohol abstinence reduces this probability and is the prerequisite for liver transplantation-the only effective therapy option at present. Elevated enzymatic activity of cytochrome P450 2E1 (CYP2E1) is known to be critically responsible for the development of ASH due to excessively high levels of reactive oxygen species (ROS) during metabolization of ethanol. Up to now, no rational drug discovery process was successfully initiated to target CYP2E1 for the treatment of ASH. METHODS: In this study, we applied a rational drug design concept to develop drug candidates (NCE) including preclinical studies. RESULTS: A new class of drug candidates was generated successfully. Two of the most promising small compounds named 12-Imidazolyl-1-dodecanol (abbr.: I-ol) and 1-Imidazolyldodecane (abbr.: I-an) were selected at the end of this process of drug discovery and developability. These new ω-imidazolyl-alkyl derivatives act as strong chimeric CYP2E1 inhibitors at a nanomolar range. They restore redox balance, reduce inflammation process as well as the fat content in the liver and rescue the physiological liver architecture of rats consuming continuously a high amount of alcohol. CONCLUSIONS: Due to its oral application and therapeutic superiority over an off-label use of the hepatoprotector ursodeoxycholic acid (UDCA), this new class of inhibitors marks the first rational, pharmaceutical concept in long-term treatment of ASH.


Assuntos
Inibidores do Citocromo P-450 CYP2E1/uso terapêutico , Citocromo P-450 CYP2E1/metabolismo , Fígado Gorduroso Alcoólico/tratamento farmacológico , Alcanos/síntese química , Alcanos/farmacologia , Alcanos/uso terapêutico , Animais , Citocromo P-450 CYP2E1/química , Inibidores do Citocromo P-450 CYP2E1/síntese química , Inibidores do Citocromo P-450 CYP2E1/farmacologia , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Feminino , Células Hep G2 , Humanos , Lipoproteínas VLDL/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Triglicerídeos/sangue , Ácido Ursodesoxicólico/análise
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