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1.
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
2.
PLoS One ; 15(8): e0237097, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810864

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder that affects a range of tissue systems, however the associated muscle weakness and fatigability can have a profound impact on quality of life. Prior studies using the limb-specific Nf1 knockout mouse (Nf1Prx1-/-) revealed an accumulation of intramyocellular lipid (IMCL) that could be rescued by a diet supplemented with L-carnitine and enriched for medium-chain fatty acids (MCFAs). In this study we used the Nf1Prx1-/- mouse to model a range of dietary interventions designed to reduce IMCL accumulation, and analyze using other modalities including in situ muscle physiology and lipid mass spectrometry. Histological IMCL accumulation was significantly reduced by a range of treatments including L-carnitine and high MCFAs alone. A low-fat diet did not affect IMCL, but did provide improvements to muscle strength. Supplementation yielded rapid improvements in IMCL within 4 weeks, but were lost once treatment was discontinued. In situ muscle measurements were highly variable in Nf1Prx1-/- mice, attributable to the severe phenotype present in this model, with fusion of the hips and an overall small hind limb muscle size. Lipidome analysis enabled segregation of the normal and modified chow diets, and fatty acid data suggested increased muscle lipolysis with the intervention. Acylcarnitines were also affected, suggestive of a mitochondrial fatty acid oxidation disorder. These data support the theory that NF1 is a lipid storage disease that can be treated by dietary intervention, and encourages future human trials.


Assuntos
Metabolismo dos Lipídeos , Força Muscular , Músculo Esquelético/metabolismo , Neurofibromatose 1/dietoterapia , Animais , Carnitina/administração & dosagem , Carnitina/uso terapêutico , Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/uso terapêutico , Feminino , Camundongos , Músculo Esquelético/fisiopatologia , Neurofibromatose 1/genética , Neurofibromina 1/genética
3.
PLoS Med ; 17(7): e1003121, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32673317

RESUMO

BACKGROUND: Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile. METHODS AND FINDINGS: We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length. CONCLUSIONS: Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.


Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Apolipoproteínas B/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Ácidos Dicarboxílicos/efeitos adversos , Ácidos Graxos/efeitos adversos , Humanos , Hipercolesterolemia/sangue , Fragmentos de Peptídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Expert Rev Cardiovasc Ther ; 18(7): 373-380, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32532162

RESUMO

INTRODUCTION: Although several lipid-lowering drugs are available, they are not sufficient for some patients. Bempedoic acid is a small molecule adenosine triphosphate-citrate lyase inhibitor indicated for the treatment of adults with hypercholesterolemia. AREAS COVERED: We performed a systematic review of the literature using PubMed database, and the following keywords were used: 'bempedoic acid,' 'hypercholesterolemia,' and 'adenosine triphosphate citrate lyase.' The chemical property, mechanism of action, pharmacokinetics, clinical efficacy, and safety of bempedoic acid are introduced in this paper. EXPERT OPINION: Bempedoic acid can modulate the metabolism of cholesterol. Clinical trials indicated that bempedoic acid could significantly reduce low-density lipoprotein cholesterol levels. Bempedoic acid was well tolerated.


Assuntos
Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Colesterol/metabolismo , Humanos , Resultado do Tratamento
8.
Nutrients ; 12(1)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936050

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. In this study, we evaluated the effects of a mixture (NCM 1921) of omega-3 butter, omega-3 beef tallow oil, omega-3 lard oil, caprylic acid, lauric acid, choline, and Fe on AD in 1-chloro-2,4-dinitrobenzene (DNCB)-treated NC/Nga mice. NCM 1921 significantly ameliorated the macroscopic and microscopic signs and reduced skin thickness and mast cell incorporation in the skin lesions of mice with DNCB-induced AD. Furthermore, it reduced serum immunoglobulin E levels; reduced the number of IgE-producing B cells, peripheral blood mononuclear cells, white blood cells, and differential white blood cells; and increased the number of lymphocytes. NCM 1921 normalized the total cell number in dorsal skin tissue, the axillary lymph node, and spleen following DNCB exposure and reduced the number of CD23+/B220+ cells in the axillary lymph node and CD3+ cells in dorsal skin tissue. Moreover, it reduced the levels of interleukin (IL)-4 and IL-13 but increased the levels of interferon-γ in anti-CD3-stimulated splenocytes. Immunohistofluorescence staining showed that NCM 1921 treatment significantly increased claudin1, filaggrin, and Sirt1 protein expressions in AD skin lesions. These results suggest that NCM 1921 could be a valuable remedy for the treatment of AD.


Assuntos
Colina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno/toxicidade , Ácidos Graxos/uso terapêutico , Animais , Colina/administração & dosagem , Citocinas/genética , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Ácidos Graxos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Baço/metabolismo
9.
JAMA ; 322(18): 1780-1788, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714986

RESUMO

Importance: Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies. Objective: To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy. Interventions: Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks. Main Outcomes and Measures: The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers. Results: Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%). Conclusions and Relevance: Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02991118.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemia Familiar Combinada/tratamento farmacológico , Idoso , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Masculino , Pessoa de Meia-Idade
10.
Molecules ; 24(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438508

RESUMO

Oral mucositis is one of the most frequent complications after chemotherapy or radiotherapy or a combination of both. There is no standard therapy for its prevention or treatment. Considering that some bee products have been found to be of value in this situation, we decided to analyze the scientific literature on the subject. Scientific publications on bee products were identified by a literature search on Pubmed, Scopus and Google Scholar. There is a lot of evidence regarding the use of honey for oral mucositis due to chemotherapy or radiotherapy or a combination of both. Unfortunately, the quality of several meta-analyses on the topic is very low. There is some evidence on propolis, a little on royal jelly and none whatsoever on pollen and other bee products like apilarnil or bee venom. Bee products such as honey, propolis and royal jelly may be well suited to be integrated into a general concept for the prevention and treatment of oral mucositis which should also include other established concepts like oral care, oral cryotherapy, topical vitamin E and low-level-laser therapy. Bee products could become an integral part in the treatment of chemotherapy, radiotherapy and radio chemotherapy. High-quality meta-analyses and further studies, especially on the combinations of various strategies, are needed.


Assuntos
Abelhas/química , Estomatite/economia , Estomatite/prevenção & controle , Administração Tópica , Animais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/uso terapêutico , Mel , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Própole/administração & dosagem , Própole/uso terapêutico , Vitamina E/administração & dosagem , Vitamina E/uso terapêutico
11.
Plast Surg Nurs ; 39(3): 87-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31441788

RESUMO

Pressure injuries are a common kind of skin lesion that may be difficult to treat. The objective of this study was to analyze the effect of hydrogel enriched with alginate, fatty acids, and vitamins A and E in the treatment of pressure injuries. This case series with 12-week follow-up included applying daily dressings with hydrogel, maintaining a photographic record, using planimetry to calculate the lesion area, and classifying the healing process using the Pressure Ulcer Scale for Healing (PUSH). In addition, exudate collection from the ulcers was performed in the beginning and after 12 weeks of treatment to determine the dosage of metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1). Of the 13 patients included in the study, 2 died and 11 were monitored for 12 weeks. Only 1 patient showed full wound healing, but all patients showed a significant 12.19% (p = .023) reduction in the lesion area. The PUSH score was also significantly reduced from 15.9 to 10.54 (p = .0052). Relative to the dosage of metalloproteinase and its inhibitor, there was a reduction in the level of MMP9 and there was no change in the level of TIMP1. This study showed that hydrogel enriched with alginate, fatty acids, and vitamins A and E provided promising results for the treatment of pressure injuries by reducing the lesion area, the general PUSH score, and the amount of MMP9 in the wounds' microenvironment.


Assuntos
Alginatos/farmacologia , Ácidos Graxos/farmacologia , Lesão por Pressão/tratamento farmacológico , Vitamina A/farmacologia , Vitamina E/farmacologia , Idoso , Alginatos/uso terapêutico , Exsudatos e Transudatos/microbiologia , Ácidos Graxos/uso terapêutico , Feminino , Seguimentos , Humanos , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Masculino , Metaloproteinase 9 da Matriz/análise , Pessoa de Meia-Idade , Lesão por Pressão/fisiopatologia , Inibidor Tecidual de Metaloproteinase-1/análise , Vitamina A/uso terapêutico , Vitamina E/uso terapêutico , Cicatrização/efeitos dos fármacos
12.
BMC Complement Altern Med ; 19(1): 175, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299973

RESUMO

BACKGROUND: Skin injury is inevitable in daily life. In recent years, with the increasing morbidity of diseases such as diabetes and metabolic disorders, chronic wounds have become a considerable challenge in clinical practice. Royal jelly, reported to have multifarious biological and physiological properties, has been used as a remedy for a variety of wounds since ancient times. However, the active components and mechanisms underlying the wound-healing properties of royal jelly are still largely unknown. METHODS: Water-soluble proteins of royal jelly were fractionated and investigated for the proliferative and migratory effects on human epidermal keratinocytes (HaCaT) in an in vitro wound healing model. The proteins present in bioactive fractions were characterised and quantified using Label-free protein quantification method. The potential functions of these proteins in biological systems were further analysed using bioinformatic tools. RESULTS: A protein fraction, mainly containing major royal jelly proteins 2 (MRJP2), MRJP3 and MRJP7, stimulated proliferative and migratory activities in HaCaT cells without visible cytotoxicity. It exerted the greatest effects on the growth of HaCaT cells in the first 48 h. Furthermore, when treated with this protein fraction, the closure rates of the in vitro scratch wound were significantly increased. Functional analysis indicated that MRJP2, MRJP3 and MRJP7 were associated with carbohydrate transport and metabolism. CONCLUSIONS: We fractionated the water-soluble proteins of royal jelly and identified one fraction (Fraction 2) that induced both proliferative and migratory effects on a human epidermal keratinocyte cell line. Major royal jelly proteins (MRJP2, MRJP3 and/or MRJP7) were speculated to possess potential wound-healing bioactivity. This is the first report that royal jelly may improve wound closure via MRJP-induced cellular proliferation and migration. These proteins may be valuable lead compounds for the development of novel wound healing medications. Our findings would facilitate better understanding of the wound repair mechanisms of royal jelly.


Assuntos
Ácidos Graxos/química , Proteínas de Insetos/uso terapêutico , Queratinócitos/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Animais , Abelhas , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ácidos Graxos/uso terapêutico , Humanos , Proteínas de Insetos/isolamento & purificação
13.
Top Companion Anim Med ; 35: 18-25, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31122683

RESUMO

The aim of this exploratory study was to evaluate the efficacy of a periophthalmic cream of a pool of fatty acids (FAG®) in association with 0.15% hyaluronate eye drops in alleviating the clinical symptoms of keratoconjunctivitis sicca (KCS) in a case series of dogs. The study was conducted on 10 dogs diagnosed with idiopathic KCS. All dogs had been previously treated with topical tobramycin alone, which had been ineffective in improving clinical signs. The affected eyes were treated with 2 applications daily of a periophthalmic cream of FAG® and 1 drop 3 times a day of 0.15% of hyaluronate eye drops for 8 weeks. Schirmer tear test I (STT I) values were recorded and ocular signs (conjunctival hyperemia, ocular discharge, corneal opacity, vascularization and pigmentation, and discomfort level) were collected, scored on a 3-point scale (grade 0, grade 1, and grade 2). Differences between scores and STT data recorded at baseline and at 8 weeks of therapy were statistically analysed. The effect of treatment was pronounced (increase in STT values by more than 4 mm/min, no signs of inflammation) in 8/18 eyes; moderate (increase in STT values of 3-4 mm/min or mild improvement in signs of corneal/conjunctival inflammation) in 3/18 eyes; and unsatisfactory in 7 of 18 eyes. Median of STT values significantly improved compared with baseline levels, while statistically significant decreases in clinical-sign scores of conjunctival hyperemia, ocular discharge, and discomfort were recorded. However, in moderate and advanced stages, reduction of neovascularization or corneal pigmentation was not observed throughout the treatment period. No noticeable adverse reactions were recorded. Preliminary results indicate that the application of periocular FAG and topical 0.15% hyaluronate eye drops may be a suitable treatment for KCS in dogs in selected cases. A larger comparative study is necessary to further confirm these findings.


Assuntos
Doenças do Cão/tratamento farmacológico , Ácidos Graxos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Ceratoconjuntivite Seca/veterinária , Animais , Cães , Ácidos Graxos/administração & dosagem , Feminino , Ácido Hialurônico/administração & dosagem , Ceratoconjuntivite Seca/tratamento farmacológico , Masculino , Soluções Oftálmicas/uso terapêutico
14.
Methodist Debakey Cardiovasc J ; 15(1): 32-38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049147

RESUMO

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins remain the first-line therapy for patients with elevated LDL-C and increased risk. However, many at-risk patients do not achieve adequate LDL-C lowering with statin monotherapy or do not tolerate statins because of side effects. Recent cardiovascular outcome trials involving ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated efficacy of nonstatin therapies in further reducing LDL-C levels and ASCVD risk. This review highlights the available nonstatin therapeutic options and explores important novel therapeutic approaches currently under development.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/uso terapêutico , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Ezetimiba/uso terapêutico , Ácidos Graxos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Pró-Proteína Convertase 9/antagonistas & inibidores , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
15.
Adv Nutr ; 10(6): 1066-1075, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31124561

RESUMO

The prevalence of type 2 diabetes (T2D) has increased rapidly. Adopting a heathy diet is suggested as one of the effective behaviors to prevent or delay onset of T2D. Dairy consumption has been recommended as part of a healthy diet, but there remains uncertainty in both the scientific community and the public about the effect of different dairy products on T2D risk. In a recent workshop, the evidence on dairy products and T2D risk was presented and discussed by a group of experts. The main conclusions from the workshop are presented in this position paper and are as follows. 1) Available evidence from large prospective cohort studies and limited randomized controlled trials (RCTs) suggests that total dairy consumption has a neutral or moderately beneficial effect on T2D risk. 2) Increasing evidence from prospective cohort studies indicates that yogurt is most strongly associated with a lower T2D risk, but evidence from RCTs is scarce. 3) Fatty acids from dairy (medium-chain, odd, and very long-chain SFAs as well as trans-palmitoleic acid) are associated with lower T2D risk and improved metabolic health, but more research is needed on studies that explore cause and effect relations to exclude the possibility that the dairy fatty acids simply serve as markers of overall dairy consumption. 4) The food matrix can be a stronger determinant of health effects than SFA content. This review further identifies research gaps in the existing knowledge and highlights key research questions that need to be addressed to better understand the impact of dairy consumption on future T2D risk.


Assuntos
Laticínios , Diabetes Mellitus Tipo 2 , Dieta , Gorduras na Dieta/uso terapêutico , Ácidos Graxos/uso terapêutico , Comportamento Alimentar , Diabetes Mellitus Tipo 2/prevenção & controle , Ácidos Graxos Monoinsaturados/uso terapêutico , Humanos , Iogurte
16.
Curr Atheroscler Rep ; 21(8): 31, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31127398

RESUMO

PURPOSE OF REVIEW: At the 2019 American College of Cardiology annual scientific sessions, major randomized clinical trials in cardiovascular disease (CVD) prevention were presented. RECENT FINDINGS: The CLEAR Wisdom trial examined the safety and efficacy of adding bempedoic acid to maximally tolerated statin for reducing low-density lipoprotein cholesterol. Post hoc analyses from the REDUCE-IT trial evaluated the efficacy of icosapent ethyl for lowering risk of total (first time and recurrent) CVD events. A sub-analysis of ODYSSEY OUTCOMES examined the effect of alirocumab on lipoprotein(a) lowering for reducing CVD risk. The CREOLE trial compared three different combination antihypertensive therapies for blood pressure lowering among black individuals in sub-Saharan Africa. The INFINITY trial examined the effect of intensive blood pressure control on progression of brain white matter changes and various components of mobility and cognitive function. Lastly, post hoc analyses from DECLARE-TIMI 58 evaluated the efficacy of dapagliflozin among patients with type 2 diabetes mellitus and heart failure or peripheral artery disease. These trials hold future promise for novel agents aimed at reducing CVD burden among high-risk patients who continue to experience CVD events despite treatment with currently available guideline-directed therapy.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Dicarboxílicos/uso terapêutico , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos/uso terapêutico , Feminino , Glucosídeos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estados Unidos
17.
Am J Chin Med ; 47(4): 727-750, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31094213

RESUMO

Cancer management is a worldwide challenge. In addition to effective cancer therapies like chemotherapy, radiotherapy and surgery, treatment based on traditional Chinese medicine (TCM) and combined TCM with western medicine has gradually gained attention in Oriental countries. One potential TCM approach using extracted fatty oils, containing fatty acids which are important active ingredients with a variety of pharmacological activities, makes significant contributions to cancer treatment. The strategies of treating cancer with the fatty oils of TCM were classified into "Fuzheng", which usually associates with improving immunity, represented by coix seed oil. The other classification is "Quxie", which relates to inducing apoptosis of cancer cells, and is represented by Brucea javanica oil. Compared with other active substances, the literature about anticancer fatty oils is relatively limited, and most of them focus on the composition and other biological activities without a systematic review. Therefore, based on the theories of "Fuzheng" and "Quxie" in TCM, in this paper, the anticancer effects of fatty oils have been reviewed. The chemical composition, anticancer mechanism, listed drugs, studying dosage form and clinical application of fatty oils have also been discussed. In summary, since there are different types and abundance of fatty oils among botanicals, anticancer effects of fatty oils can be achieved through two TCM theory-based strategies. We hoped that this review paper can reveal the anticancer potential of fatty oils and provide a reference for future related studies.


Assuntos
Medicamentos de Ervas Chinesas/química , Ácidos Graxos/uso terapêutico , Glicerol/uso terapêutico , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico , Óleos Vegetais/química , Óleos Vegetais/uso terapêutico , Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Glicerol/química , Glicerol/isolamento & purificação , Glicerol/farmacologia , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Fitoterapia , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia
18.
Cells ; 8(5)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083403

RESUMO

HIF-1 serves as an important regulator in cell response to hypoxia. Due to its key role in promoting tumor survival and progression under hypoxia, HIF-1 has become a promising target of cancer therapy. Thus far, several HIF-1 inhibitors have been identified, most of which are from synthesized chemical compounds. Here, we report that ALM (ActinoLactoMycin), a compound extracted from metabolites of Streptomyces flavoretus, exhibits inhibitory effect on HIF-1α. Mechanistically, we found that ALM inhibited the translation of HIF-1α protein by suppressing mTOR signaling activity. Treatment with ALM induced cell apoptosis and growth inhibition of cancer cells both in vitro and in vivo in a HIF-1 dependent manner. More interestingly, low dose of ALM treatment enhanced the anti-tumor effect of Everolimus, an inhibitor of mTOR, suggesting its potential use in combination therapy of tumors, especially solid tumor patients. Thus, we identified a novel HIF-1α inhibitor from the metabolites of Streptomyces flavoretus, which shows promising anti-cancer potential.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ácidos Graxos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lactonas/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/uso terapêutico , Everolimo/farmacologia , Everolimo/uso terapêutico , Ácidos Graxos/uso terapêutico , Humanos , Lactonas/uso terapêutico , Camundongos Endogâmicos BALB C , Camundongos Nus , Processos Neoplásicos , Células PC-3 , Transdução de Sinais/efeitos dos fármacos , Streptomyces/metabolismo , Serina-Treonina Quinases TOR/metabolismo
19.
Am J Clin Nutr ; 109(Suppl_7): 852S-871S, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982869

RESUMO

BACKGROUND: Proper nutrition during early life is critical for growth and development. OBJECTIVES: The aim was to describe systematic reviews conducted by the Nutrition Evidence Systematic Review team for the USDA and the Department of Health and Human Services Pregnancy and Birth to 24 Months Project to answer the following: What is the relation between 1) timing of introduction of complementary foods and beverages (CFBs) or 2) types and/or amounts of CFBs consumed and micronutrient status (iron, zinc, vitamin D, vitamin B-12, folate, and fatty acid status)? METHODS: A literature search identified articles from developed countries published from January 1980 to July 2016 that met the inclusion criteria. Data were extracted and risk of bias assessed. Evidence was qualitatively synthesized to develop a conclusion statement, and the strength of the evidence was graded. RESULTS: Nine articles addressed the timing of CFB introduction and 31 addressed types or amounts or both of CFBs. Moderate evidence suggests that introducing CFBs at age 4 mo instead of 6 mo offers no advantages or disadvantages in iron status among healthy full-term infants. Evidence is insufficient on the timing of CFB introduction and other micronutrient status outcomes. Strong evidence suggests that CFBs containing iron (e.g., meat, fortified cereal) help maintain adequate iron status or prevent deficiency in the first year among infants at risk of insufficient iron stores or low intake. Benefits for infants with sufficient iron stores (e.g., infant formula consumers) are less clear. Moderate evidence suggests that CFBs containing zinc (e.g., meat, fortified cereal) support zinc status in the first year and CFB fatty acid composition influences fatty acid status. Evidence is insufficient with regard to types and amounts of CFBs and vitamin D, vitamin B-12, and folate status, or the relation between lower-iron-containing CFBs and micronutrient status. CONCLUSIONS: Several conclusions on CFBs and micronutrient status were drawn from these systematic reviews, but more research that addresses specific gaps and limitations is needed.


Assuntos
Deficiências Nutricionais/sangue , Dieta , Comportamento Alimentar , Alimentos Infantis , Fenômenos Fisiológicos da Nutrição do Lactente , Micronutrientes/sangue , Estado Nutricional , Bebidas , Aleitamento Materno , Deficiências Nutricionais/etiologia , Deficiências Nutricionais/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Ácidos Graxos/uso terapêutico , Alimentos Fortificados , Humanos , Lactente , Fórmulas Infantis , Saúde do Lactente , Micronutrientes/administração & dosagem , Micronutrientes/uso terapêutico , Oligoelementos/administração & dosagem , Oligoelementos/sangue , Oligoelementos/uso terapêutico , Vitaminas/administração & dosagem , Vitaminas/sangue , Vitaminas/uso terapêutico
20.
J Affect Disord ; 252: 334-349, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30999090

RESUMO

BACKGROUND: Nutraceuticals are a group of compounds of growing interest for mental health professionals. Given the implication of certain nutrients in the onset of bipolar disorder, it has been hypothesized that nutraceuticals might be effective in improving symptoms of the condition (i.e. mania or depression). Our systematic review aimed to evaluate the effectiveness of adjunctive nutraceuticals compared to placebo. METHODS: We searched the following databases from inception to February 2019: Web of Science, CINAHL, Embase, and PsycINFO. We included only original randomized controlled trials written in English, testing the efficacy of nutraceuticals in add-on to standard care, compared to placebo, in patients with bipolar disorder. RESULTS: After identifying 6584 potentially relevant publications, we finally included 25 studies, among which six used fatty acids, seven micronutrients, seven amino acids. One study tested probiotics, while in four trials a combination of different types of nutraceuticals was used. Even if some compounds have shown promising results (i.e. fatty acids and N-acetyl cysteine for depression, amino acid drinks and folic acid for mania), the majority of nutraceuticals did not cause significant improvements in comparison to placebo. LIMITATIONS: We could not perform a meta-analysis due to the high heterogeneity of trials, which were also affected by some methodological caveats. CONCLUSIONS: Evidence regarding the efficacy of adjunctive nutraceuticals in bipolar disorder is inconsistent. Nevertheless, they appear generally free from relevant side effects. Well-designed trials are needed to further explore the potential role of nutraceuticals in different mood episodes.


Assuntos
Aminoácidos/uso terapêutico , Transtorno Bipolar/terapia , Suplementos Nutricionais , Ácidos Graxos/uso terapêutico , Micronutrientes/uso terapêutico , Transtorno Bipolar/psicologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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