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1.
Rev Col Bras Cir ; 47: e20202537, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33053063

RESUMO

OBJECTIVE: to analyze the effect of vertical gastrectomy on lipid profile and cardiometabolic risk in young women, preoperatively and 6 months after the operation. METHODS: retrospective study, encompassing medical record reviews of women's charts, preoperatively and in six months after the operation. Data collection was performed in the second half of 2015, using a review protocol with questions on the clinical-laboratory profile, anthropometric and laboratory classification of dyslipidemias. Descriptive and inferential analysis were used to treat the variables, using measures of variance, association and linear regression. RESULTS: we analyzed medical records of 114 women undergoing vertical gastrectomy, with a mean age of 33.82±10.92, and with complete high school education. There was a significant reduction of anthropometric data, as well as serum lipid values, six months after the surgical procedure. The coefficients of determination and the results of linear regression, showed that the reduction in serum triglyceride values and increase in high-density lipoprotein have a direct impact on the reduction of the cardiometabolic risk. Regarding the laboratory classification of dyslipidemias, it was observed that the majority presented a significant reduction at the six-month follow-up. Mixed hyperlipidemia showed no significant reduction. The categorized cardiometabolic risk showed a significant reduction in women at risk before vertical gastrectomy. CONCLUSION: at the six-month follow-up, vertical gastrectomy was effective in reducing the serum lipid profile and the cardiometabolic risk of young women when compared to the preoperative data. There was also a different improvement in the laboratory classification of dyslipidemias at the six-month follow-up after the surgical procedure.


Assuntos
Gastrectomia/efeitos adversos , Lipídeos/sangue , Obesidade Mórbida/cirurgia , Doenças Cardiovasculares , Feminino , Humanos , Estudos Retrospectivos , Perda de Peso
2.
Medicine (Baltimore) ; 99(40): e22249, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019400

RESUMO

BACKGROUND: To comprehensively evaluate the treatment efficacy and safety of silymarin for patients with glucose/lipid metabolic dysfunction using a meta-analysis. METHODS: A systematic literature search in PubMed, EMBASE and Cochrane Library databases was performed up to October 1, 2019. STATA 13.0 software was used to estimate pooled standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Sixteen studies involving 1358 patients were identified. Overall meta-analysis showed that compared with control, silymarin significantly reduced levels of fasting blood glucose (SMD: -1.27, 95% CI = [-1.78, -0.76]; P < .001), homeostatic model assessment for insulin resistance (SMD: -0.41, 95% CI = [-0.70, -0.12]; P = .005), hemoglobin A1c (SMD: -1.88, 95% CI = [-2.57, -1.20]; P < .001), total cholesterol (SMD: -1.13, 95% CI = [-1.82, -0.77]; P < .001), triglyceride (SMD: -0.37, 95% CI = [-0.69, -0.05]; P = .025), low-density lipoprotein-cholesterol (SMD: -1.30, 95% CI = [-1.93, -0.67]; P < .001), C-reactive protein (SMD: -0.63, 95% CI = [-1.01, -0.27]; P = .001), and increased high-density lipoprotein-cholesterol (SMD: 0.17, 95% CI = [0.05, 0.29]; P = .005), but had no impacts on function indicators of liver and kidney (alanine transaminase, aspartate aminotransferase, creatinine phosphokinase, creatinine) and the complication rate. Subgroup analyses indicated that insulin (which was negative in overall analysis) was significantly decreased in patients undergoing silymarin monotherapy (SMD: -2.03, 95% CI = [-3.03, -1.04]; P = .044) for more than 3 months (SMD: -0.01, 95% CI = [-0.25, -0.24]; P = .035). CONCLUSION: Supplementation of silymarin may be effective and safe for the management of diabetes mellitus and hyperlipidemia.


Assuntos
Antioxidantes/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Silimarina/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Biomarcadores Farmacológicos , Glicemia/análise , Proteína C-Reativa/análise , Estudos de Casos e Controles , Hemoglobina A Glicada , Humanos , Resistência à Insulina/fisiologia , Testes de Função Renal , Lipídeos/sangue , Testes de Função Hepática , Silimarina/administração & dosagem , Silimarina/efeitos adversos
3.
Medicine (Baltimore) ; 99(40): e22266, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019401

RESUMO

INTRODUCTION: Gestational hyperinsulinism is a metabolic disease which is widely concerned at home and abroad. It is a clinical consensus that the embryo implantation ability of patients with hyperinsulinemia is decreased and the abortion rate after implantation is high. The treatment of gestational hyperinsulinism with Multiple dietary fiber diets has been proven. However, due to the lack of evidence, there is no specific method or recommendation, it is necessary to carry out a systematic evaluation of Multiple dietary fiber diet, to provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to August 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and CNKI. Primary outcomes: Fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance, glycosylated hemoglobin. Additional outcomes: Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), triglycerides (TG), total serum cholesterol (TC). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews (SR) of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of Multiple dietary fiber diet interventions in the treatment of gestational hyperinsulinism. CONCLUSION: The SR of this study will summarize the current published evidence of Multiple dietary fiber for the treatment of gestational hyperinsulinism, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a SR, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRA NETWORK (OSF) REGISTRATION NUMBER: August 19, 2020. osf.io/tbc7z. (https://osf.io/tbc7z).


Assuntos
Fibras na Dieta/uso terapêutico , Hiperinsulinismo/dietoterapia , Complicações na Gravidez/dietoterapia , Glicemia/fisiologia , Fibras na Dieta/administração & dosagem , Fibras na Dieta/efeitos adversos , Feminino , Hemoglobina A Glicada/análise , Humanos , Resistência à Insulina/fisiologia , Lipídeos/sangue , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
4.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
5.
Drugs Today (Barc) ; 56(9): 573-582, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33025951

RESUMO

Bempedoic acid is a new, first-in-class oral ATP-citrate lyase (ACLY) inhibitor that has to be converted to its CoA thioester before it inhibits ACLY. This conversion only occurs in the liver and not in skeletal muscle. This may explain why, unlike the statins, bempedoic acid does not cause myalgia. Bempedoic acid given at a dosage of 180 mg orally once daily produces a highly significant reduction in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and importantly also in high-sensitivity C-reactive protein. It has recently been approved by both the Food and Drug Administration (FDA) and the European Commission for use in adult patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease who require additional lowering of LDL-C, and for the treatment of adults with primary hypercholesterolemia (heterozygous familial and nonfamilial) or mixed dyslipidemia, respectively.


Assuntos
ATP Citrato (pro-S)-Liase/antagonistas & inibidores , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Lipídeos/sangue , Humanos
6.
N Engl J Med ; 383(14): 1317-1327, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865373

RESUMO

BACKGROUND: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS: A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Adolescente , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Heterozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/genética , Lipídeos/sangue , Masculino , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(37): e22171, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925785

RESUMO

The correlations between retinal vessel distribution, anterior chamber depth (ACD) and other myopic eye structural parameters remains elusive. This study aims to investigate retinal vasculature and eye structure correlations in healthy and myopic eyes of Chinese young adults.In this cross-sectional study, 181 eyes (97 adults) were recruited. Macular and peripapillary vasculature was quantified by optical coherence tomography angiography. Correlations between retinal vasculature and eye structure were analyzed using multivariable linear regression.There were significant differences in ACD, spherical equivalent, axial length (AL), superficial macular vascular density (MVD), peripapillary vascular density (PVD) and circumference of foveal avascular zone (FAZ) among emmetropia, low-myopia, moderate-myopia, and high-myopia groups (both P < 0.05). Furthermore, ACD had significant positive correlation with AL and FAZ, but negative correlation with PVD. MVD also had a negative correlation with AL (beta = -0.247, P < .001). In addition, there was a significant negative correlation between circumference of the FAZ and spherical equivalent as well as central subfield thickness (beta = -0.20, P = .005; beta = -0.334, P < .001, respectively).The degree of myopia affected ACD, MVD, PVD, and circumference of the FAZ in eyes of young healthy adults. Meanwhile, ACD has a positive, while retinal vascular system measurements have a negative correlation with increasing severity of myopia.


Assuntos
Olho/irrigação sanguínea , Olho/patologia , Miopia/patologia , Vasos Retinianos/patologia , Adolescente , Adulto , Fatores Etários , Glicemia , Capilares/patologia , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Tomografia de Coerência Óptica , Adulto Jovem
8.
Medicine (Baltimore) ; 99(37): e22202, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925796

RESUMO

Metabolic syndrome (MetS), mainly caused by intra-abdominal fat (IAF) accumulation, is an important risk factor for cardiovascular disease. The prevalence of MetS increases rapidly after the age of 40 years, and it is presumed that there is a substantial proportion of MetS in younger age groups. However, the association of IAF with MetS in adults aged 20 to 30 years has not been fully investigated.This study aimed to determine the prevalence of MetS and to verify whether IAF accumulation is associated with other MetS-related metabolic disorders including dyslipidemia, high blood pressure, and high blood glucose among the Japanese population in their 20s.In this cross-sectional study, IAF area (IAFA) and MetS-related metabolic parameters were evaluated in university students in their 20s (n = 1822, 21.5 ±â€Š1.5 years). IAFA was measured using a non-invasive device, DUALSCAN, which can be readily measured through the dual impedance method. The participants were divided into four groups according to IAFA: 0-49.9, 50-74.9, 75-99.9, and ≥100 cm.MetS was prevalent in 3.3% and 0.0% of the males and females, respectively, according to the Japanese criteria of MetS. The sex- and lifestyle-adjusted odds ratios (ORs) for the three metabolic component levels of Mets were elevated in the larger IAFA groups compared to the smallest IAFA group, according to the level of IAFA. The levels particularly increased in participants with abdominal obesity, defined by both, IAFA and waist circumference rather than by waist circumference alone.IAF accumulation was significantly associated with MetS-related metabolic disorders in young adults. An evaluation of IAFA may contribute to the early prediction of the risk of developing MetS in the future.


Assuntos
Síndrome Metabólica/epidemiologia , Obesidade Abdominal/epidemiologia , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Pesos e Medidas Corporais , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Gordura Intra-Abdominal/fisiopatologia , Estilo de Vida , Lipídeos/sangue , Masculino , Fatores Sexuais , Circunferência da Cintura , Adulto Jovem
9.
Medicine (Baltimore) ; 99(35): e21722, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871891

RESUMO

BACKGROUND: In recent years, the role of vitamin D (VD) as a protective factor in cardiovascular disease has been recognized. Thus, there is a need to study the effect of vitamin D supplementation in the control of different cardiovascular risk factors and metabolic syndrome, especially in young populations where few studies have been conducted. METHODS: Pilot study of a randomized, parallel two-arm, triple-blind clinical controlled trial in 150 adolescents and young adults in the city of Bucaramanga-Colombia. The intervention group will receive 1000 IU of VD and the control group 200 IU of VD daily for 15 weeks. The main outcomes are: serum calcifediol levels (25(OH) D), body mass index and lipid profile; secondary outcomes are complementary to the previous ones (skin folds, waist-hip ratio). Other variables will be analyzed such as assessment of dietary intake, physical activity, sun exposure, cigarette and tobacco consumption and compliance with VD supplementation. DISCUSSION: This study is innovative since there is little evidence from clinical trials in adolescents and young adults; similar studies are not known in our context. The results of this study may facilitate the recommendation of oral vitamin D supplementation in the population of interest. In addition, it is a low-cost and easy-to-apply intervention that could contribute to the formulation and implementation of health policies. TRIAL REGISTRATION: NCT04377386.


Assuntos
Índice de Massa Corporal , Calcifediol/sangue , Lipídeos/sangue , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Administração Oral , Adolescente , Colômbia , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , Pregas Cutâneas , Relação Cintura-Quadril , Adulto Jovem
10.
Medicine (Baltimore) ; 99(33): e21566, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872008

RESUMO

Metabolic syndrome (MetS) refers to the pathological state of metabolic disorders in the body's proteins, fats, carbohydrates and other substances. MetS is a systemic metabolic disease. Periodontal disease is also a part of systemic inflammatory diseases. Among Chinese patients with middle-aged and elderly MetS, the periodontal morbidity is very high, which is due to the involvement of inflammatory mediators in the pathogenesis of MetS and periodontal disease. The latter may also be a risk factor for the former's morbidity and promotion of disease progression. At present, there are not many investigations and studies on periodontal examination data and periodontal disease prevalence of patients with MetS. Coal mine workers, especially coal mine underground workers, have different work natures and different working environments. See related report.We will collect the clinical diagnosis and treatment information of the enrolled patients. We will focus on checking the incidence of periodontal disease and recording. Establish a database, check every 10 medical records, and make corrections in time to ensure data accuracy. We will popularize oral hygiene knowledge for the included patients and guide them to brush their teeth correctly and how to use dental floss. We will perform periodontal examination on the patients' teeth by site and record the plaque index, gingival sulcus bleeding index, periodontal pocket exploration depth and other indicators. We will repeat the above inspection items and record in the second and fourth weeks of the experiment.This study will explore the correlation between periodontal disease and MetS of coal mine workers. We aim to clarify the role and mechanism of MetS in the occurrence and development of periodontal diseases, guide the prevention of periodontal diseases, and thus reduce the prevalence of periodontal diseases. TRIAL REGISTRATION:: ClinicalTrials.gov, ChiCTR2000034177, Registered on 27 June 2020.


Assuntos
Carvão Mineral , Síndrome Metabólica/epidemiologia , Mineradores/estatística & dados numéricos , Doenças Periodontais/epidemiologia , Adulto , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Índice Periodontal , Prevalência , Fatores de Risco , Fumar/epidemiologia , Adulto Jovem
11.
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
12.
Medicine (Baltimore) ; 99(33): e21498, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871996

RESUMO

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid.We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens:The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P < .001). With respect to different chemotherapy regimens, FEC had less side effects on lipid profiles (TG (P = .006), high-density lipoprotein (HDL-C) (P < .001), and LDL-C (P < .001)) than TC regimen and AC-T and EC-T regimen. Also, the incidence of newly diagnosed dyslipidemia after chemotherapy was lower in FEC group than TC group and AC-T and EC-T group (P < .001). Additionally, the magnitude of the alterations in lipid profiles (TG, TC, HDL-C, and LDL-C) was greater in premenopausal patients than that of the postmenopausal patients (P = .004; P < .001; P = .002; P = .003, respectively). Moreover, after adjusting for multiple baseline covariates, anthracycline-plus-taxane-based regimens (AC-T and EC-T) were still statistically associated with a high level of TG (P = .004) and a low level of HDL-C (P = .033) after chemotherapy compared with FEC regimen. Also, body mass index (BMI) > 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P < .001; P = .036; P = .012; P = .048, respectively).BC patients receiving chemotherapy may have elevated lipid profiles, and anthracycline-based regimen had less side effects on lipid profiles compared with regimens containing taxane. Therefore, it is necessary to take lipid metabolism into consideration when making chemotherapy decisions and dyslipidemia prevention and corresponding interventions are indispensable during the whole chemotherapy period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Lipídeos/sangue , Adulto , Idoso , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
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
14.
PLoS Biol ; 18(9): e3000870, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32986697

RESUMO

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.


Assuntos
Envelhecimento/sangue , Lipidômica , Lipídeos/sangue , Obesidade/metabolismo , Caracteres Sexuais , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Menopausa/sangue , Pessoa de Meia-Idade , Circunferência da Cintura
15.
Nat Commun ; 11(1): 4643, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938935

RESUMO

Time-restricted feeding (TRF) improves metabolism independent of dietary macronutrient composition or energy restriction. To elucidate mechanisms underpinning the effects of short-term TRF, we investigated skeletal muscle and serum metabolic and transcriptomic profiles from 11 men with overweight/obesity after TRF (8 h day-1) and extended feeding (EXF, 15 h day-1) in a randomised cross-over design (trial registration: ACTRN12617000165381). Here we show that muscle core clock gene expression was similar after both interventions. TRF increases the amplitude of oscillating muscle transcripts, but not muscle or serum metabolites. In muscle, TRF induces rhythmicity of several amino acid transporter genes and metabolites. In serum, lipids are the largest class of periodic metabolites, while the majority of phase-shifted metabolites are amino acid related. In conclusion, short-term TRF in overweight men affects the rhythmicity of serum and muscle metabolites and regulates the rhythmicity of genes controlling amino acid transport, without perturbing core clock gene expression.


Assuntos
Aminoácidos/sangue , Ritmo Circadiano/genética , Jejum , Lipídeos/sangue , Músculo Esquelético/metabolismo , Adulto , Relógios Circadianos/genética , Estudos Cross-Over , Expressão Gênica , Humanos , Metabolismo dos Lipídeos , Masculino , Músculo Esquelético/fisiologia , Sobrepeso/dietoterapia , Sobrepeso/metabolismo
16.
Medicine (Baltimore) ; 99(38): e22032, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957320

RESUMO

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a metabolic disease with widespread concern in the world. It has the characteristics of high incidence rate and high disability rate, which seriously affects economic and social development. large dose herb Rhizoma Coptidis (Huanglian) and Scutellaria (Huangqin) or compound prescription contain large dose Huanglian and Huanglian for treatment of T2DM has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Coptidis and Scutellaria and provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WanFang, VIP medicine information, and China National Knowledge Infrastructure. Primary outcomes: fasting blood-glucose (FBG), 2 Hours Postprandial Blood Glucose (2hPBG), Glycosylated hemoglobin A1c (HbA1c). additional outcomes: Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), triglycerides (TG), total serum cholesterol (TC). Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose Huanglian and Huangqin intervention for people with T2DM. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose Huanglian and Huangqin for the treatment of T2DM, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER: July 21, 2020. osf.io/b6r3z. (https://osf.io/b6r3z).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Scutellaria , Glicemia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Hemoglobina A Glicada , Estilo de Vida Saudável , Humanos , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
17.
Medicine (Baltimore) ; 99(38): e22036, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957321

RESUMO

Studies about the effects of metabolically healthy obesity on cardiovascular disease (CVD) have yielded conflicting results. These heterogeneous results could be due to the limited usefulness of BMI in measuring general adiposity, as body mass index (BMI) does not accurately reflect body composition. This study aimed to evaluate the effect of body shape on CVD outcomes across different obesity phenotypes, and to provide an explanation for the heterogeneous effects of metabolically healthy obese (MHO) phenotype on CVD.We analyzed data from the Korean Genome and Epidemiology Study, a population-based cohort study conducted between 2001 and 2012. We divided the participants into 4 groups: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). To assess body shape, we calculated the z-score of the log-transformed a body shape index (LBSIZ). We computed Pearson correlation coefficients to examine the association of LBSIZ with muscle mass index, percentage of total fat mass (%Total FM), and percentage of abdominal fat mass (%Abdominal FM). We also used Cox proportional hazards regression to evaluate the effect of LBSIZ on CVD events according to the obesity phenotypes.A total of 9460 participants were assessed in this study. The incidence of CVD was 8.53 cases per 1000 person-year. LBSIZ showed strong positive correlation with %Total FM and %Abdominal FM, but negative correlation with muscle mass index. In Cox regression, MHO individuals did not show increased risk of CVD compared with MHNO individuals (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.96-1.73). However, MHO individuals in the 3rd (HR, 2.40; 95% CI, 1.28-4.51) and 4th (HR, 3.67; 95% CI, 1.99-6.74) quarters of LBSIZ showed significantly higher risk of CVD compared with MHNO individuals in the 1st quarter of LBSIZ. Moreover, LBSIZ showed a linear relationship with CVD among MHO individuals.While the MHO individuals showed similar CVD risk to the MHNO individuals, CVD risk increases with LBSIZ among the MHO individuals. LBSIZ appears to be a useful measure for CVD risk assessment in clinical practice and epidemiologic studies, especially for MHO patients.


Assuntos
Composição Corporal/fisiologia , Doenças Cardiovasculares/epidemiologia , Obesidade Metabolicamente Benigna/epidemiologia , Obesidade Metabolicamente Benigna/patologia , Adiposidade , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Glicemia , Índice de Massa Corporal , Pesos e Medidas Corporais , Fumar Cigarros/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos
18.
PLoS One ; 15(8): e0237739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817629

RESUMO

OBJECTIVE: To assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients. METHODS: We performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/µL, not starting c-ART; and group B, CD4<500 cells/µL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time. RESULTS: The study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30-43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values. CONCLUSIONS: In treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.


Assuntos
Aterosclerose/sangue , Biomarcadores/sangue , Infecções por HIV/sangue , Lipídeos/sangue , Adulto , Antirretrovirais/administração & dosagem , Antirretrovirais/sangue , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Aterosclerose/tratamento farmacológico , Aterosclerose/virologia , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Colesterol/sangue , Grupos Controle , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/virologia , Lipoproteínas LDL/sangue , Masculino , Estudos Prospectivos
19.
Chem Biol Interact ; 330: 109234, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32860823

RESUMO

Cisplatin is an antineoplastic drug well recognized for its success in the battle against several types of cancer in adult, juvenile, and child populations. Meanwhile, this drug is also famous due to its serious side effects, such as hepatotoxicity. This study evaluated the hepatoprotective effectiveness of Diphenyl Diselenide (PhSe)2 and Ebselen in a model of cisplatin-induced toxicity in juvenile rats. Juvenile Wistar rats received a single intraperitoneal (i.p) injection of cisplatin (6 mg/kg) or saline solution, at postnatal day (PND) 21. Ebselen (11 mg/kg) or (PhSe)2 (12 mg/kg) was intragastrically (i.g) administered in rats from PND 21 to PND 25. At PND 26, the blood and liver were collected for the biochemistry assays. A single administration of cisplatin was enough to alter the makers of hepatic function (an increase of AST activity) and the blood lipid profile (an increase of cholesterol and triglycerides, TG). The cisplatin-induced metabolic disruption was demonstrated by the increase of hepatic glycogen and TG contents and hexokinase, glucose-6-phosphatase, and tyrosine aminotransferase activities; a decrease of citrate synthase activity and the levels of GLUT-2. Cisplatin-induced hepatic oxidative stress was characterized by an increase in reactive oxygen species, TBARS, protein carbonyl, and Nox levels as well as the decrease in NPSH levels. Ebselen and (PhSe)2 were effective against all alterations caused by this chemotherapy medication. The present findings highlight the (PhSe)2 and Ebselen similar hepatoprotective effectiveness against cisplatin-induced disruption of metabolic homeostasis and redox balance in juvenile rats.


Assuntos
Azóis/farmacologia , Derivados de Benzeno/farmacologia , Cisplatino/toxicidade , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Lipídeos/sangue , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos
20.
Nat Commun ; 11(1): 4279, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855410

RESUMO

Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolipid synthesis and efflux of Cav-1-sphingolipid particles containing mitochondrial proteins and lipids. We also demonstrate, using a prostate cancer syngeneic RM-9 mouse model and established cell lines, that this Cav-1-sphingolipid program evidences a metabolic vulnerability that is targetable to induce lethal mitophagy as an anti-tumor therapy.


Assuntos
Caveolina 1/metabolismo , Neoplasias da Próstata/metabolismo , Esfingolipídeos/metabolismo , Idoso , Animais , Caveolina 1/sangue , Caveolina 1/genética , Linhagem Celular Tumoral , Ceramidas/metabolismo , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica , Glicoesfingolipídeos/biossíntese , Humanos , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Pirrolidinas/farmacologia , Esfingomielinas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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