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1.
Adv Exp Med Biol ; 1274: 55-69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32894507

RESUMO

Leukotrienes (LTs) are potent lipid mediators that exert a variety of functions, ranging from maintaining the tone of the homeostatic immune response to exerting potent proinflammatory effects. Therefore, LTs are essential elements in the development and maintenance of different chronic diseases, such as asthma, arthritis, and atherosclerosis. Due to the pleiotropic effects of LTs in the pathogenesis of inflammatory diseases, studies are needed to discover potent and specific LT synthesis inhibitors and LT receptor antagonists. Even though most clinical trials using LT inhibitors or antagonists have failed due to low efficacy and/or toxicity, new drug development strategies are driving the discovery for LT inhibitors to prevent inflammatory diseases. A newly important detrimental role for LTs in comorbidities associated with metabolic stress has emerged in the last few years and managing LT production and/or actions could represent an exciting new strategy to prevent or treat inflammatory diseases associated with metabolic disorders. This review is intended to shed light on the synthesis and actions of leukotrienes, the most common drugs used in clinical trials, and discuss the therapeutic potential of preventing LT function in obesity, diabetes, and hyperlipidemia.


Assuntos
Comorbidade , Antagonistas de Leucotrienos/uso terapêutico , Leucotrienos/metabolismo , Doenças Metabólicas/complicações , Doenças Metabólicas/prevenção & controle , Estresse Fisiológico , Asma , Aterosclerose , Humanos
2.
AIDS ; 34(12): 1771-1774, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773476

RESUMO

: We performed an observational prospective monocentric study in patients living with HIV (PLWH) diagnosed with COVID-19. Fifty-four PLWH developed COVID-19 with 14 severe (25.9%) and five critical cases (9.3%), respectively. By multivariate analysis, age, male sex, ethnic origin from sub-Saharan Africa and metabolic disorder were associated with severe or critical forms of COVID-19. Prior CD4 T cell counts did not differ between groups. No protective effect of a particular antiretroviral class was observed.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por HIV/complicações , Pneumonia Viral/epidemiologia , Adulto , África ao Sul do Saara/etnologia , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Infecções por Coronavirus/etnologia , Feminino , França/epidemiologia , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Logísticos , Masculino , Doenças Metabólicas/complicações , Pessoa de Meia-Idade , Análise Multivariada , Pandemias , Pneumonia Viral/etnologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco
3.
Medicine (Baltimore) ; 99(27): e21140, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629750

RESUMO

INTRODUCTION: Treating blood stasis is effective in treating obesity and metabolic diseases in traditional Korean medicine. The aim of this prospective observational study is to determine the effectiveness of the diagnosis index for metabolic diseases with blood stasis by analyzing clinical data and blood samples. METHODS AND ANALYSIS: We will perform a prospective observational study. Participants who meet the inclusion criteria will be recruited from the Dongguk university Ilsan Oriental hospital. The outcomes are resistin, serum amyloid P component, C-reactive protein, D-dimer, and blood stasis scores. In addition, the blood pressure, ankle-brachial pressure index, brachial-ankle pulse wave velocity, body mass index, waist circumference, and levels of blood lipid will be assessed. DISCUSSION: Through this study, we could collect specific data for diagnosing metabolic diseases with blood stasis. Therefore, the findings of this study will provide a summary of the current state of evidence regarding the effectiveness of the diagnosis index in managing metabolic disease with blood stasis. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of the Dongguk University Ilsan Oriental Hospital (DUIOH-2018-09-001-007). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print. TRIAL REGISTRATION NUMBER: Clinical Research Information Service: KCT0003548.


Assuntos
Medicina Tradicional Coreana/métodos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/terapia , Língua/irrigação sanguínea , Adulto , Idoso , Índice Tornozelo-Braço/métodos , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Feminino , Humanos , Lipídeos/sangue , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Onda de Pulso/métodos , República da Coreia/epidemiologia , Língua/patologia , Circunferência da Cintura/fisiologia
4.
BMC Med ; 18(1): 220, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32664957

RESUMO

BACKGROUND: In women of reproductive age, polycystic ovary syndrome (PCOS) constitutes the most frequent endocrine disorder. Women with PCOS are considered to typically belong to an age and sex group which is at lower risk for severe COVID-19. MAIN BODY: Emerging data link the risk of severe COVID-19 with certain factors such as hyper-inflammation, ethnicity predisposition, low vitamin D levels, and hyperandrogenism, all of which have known direct associations with PCOS. Moreover, in this common female patient population, there is markedly high prevalence of multiple cardio-metabolic conditions, such as type 2 diabetes, obesity, and hypertension, which may significantly increase the risk for adverse COVID-19-related outcomes. This strong overlap of risk factors for both worse PCOS cardio-metabolic manifestations and severe COVID-19 should be highlighted for the clinical practice, particularly since women with PCOS often receive fragmented care from multiple healthcare services. Comprehensively informing women with PCOS regarding the potential risks from COVID-19 and how this may affect their management is also essential. CONCLUSION: Despite the immense challenges posed by the COVID-19 outbreak to the healthcare systems in affected countries, attention should be directed to maintain a high standard of care for complex patients such as many women with PCOS and provide relevant practical recommendations for optimal management in the setting of this fast moving pandemic.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome do Ovário Policístico/complicações , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hiperandrogenismo/complicações , Hiperandrogenismo/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome do Ovário Policístico/epidemiologia , Prevalência , Fatores de Risco
6.
Life Sci ; 255: 117843, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32464123

RESUMO

Metabolic diseases, such as obesity and type 2 diabetes, are known risk factors for cardiovascular (CV) diseases. Thus, patients with those comorbidities could be at increased risk of experiencing cardiotoxicity related to treatment with Anthracyclines and the other new generation targeted anticancer drugs. However, investigations addressing the mechanisms underlying the development of CV complications and poor outcome in such cohort of patients are still few and controversial. Given the importance of a personalized approach against chemotherapy-induced cardiomyopathy, this review summarizes our current knowledge on the pathophysiology of chemotherapy-induced cardiomyopathy and its association with obesity and type 2 diabetes. Along with clinical evidences, future perspectives of preclinical research around this field and its role in addressing important open questions, including the development of more proactive strategies for prevention, and treatment of cardiotoxicity during and after chemotherapy in the presence of metabolic diseases, is also presented.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Doenças Metabólicas/complicações , Animais , Antineoplásicos/administração & dosagem , Cardiotoxicidade/fisiopatologia , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Neoplasias/tratamento farmacológico , Obesidade/complicações , Fatores de Risco
7.
Einstein (Sao Paulo) ; 18: eAO5150, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32159605

RESUMO

OBJECTIVE: To verify the association of obesity and infertility related to anovulatory issues. METHODS: This case-control study was carried out with 52 women, aged 20 to 38 years, divided into two groups (infertile - cases - and fertile - control), seen at outpatient clinics, in the period from April to December, 2017. RESULTS: We found significant evidence that obesity negatively affects women's fertility (p=0.017). The group of infertile women was 7.5-fold more likely to be obese than fertile women. CONCLUSION: Strategies that encourage weight control are indicated for women with chronic anovulation, due to hight metabolic activity of adipose tissue.


Assuntos
Anovulação/etiologia , Infertilidade Feminina/etiologia , Obesidade/complicações , Adulto , Anovulação/metabolismo , Anovulação/fisiopatologia , Antropometria , Estudos de Casos e Controles , Exercício Físico/fisiologia , Feminino , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/fisiopatologia , Doenças Metabólicas/complicações , Doenças Metabólicas/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Fatores de Risco , Comportamento Sedentário , Inquéritos e Questionários , Adulto Jovem
8.
Clin Dermatol ; 38(1): 79-85, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197751

RESUMO

Recognizing the skin manifestations of metabolic and endocrine disorders, many of which may have potentially lethal complications, is important for dermatologists and other clinicians. The skin can be a window into a patient's internal health, and cutaneous manifestations can facilitate early diagnosis and intervention of potentially life-altering systemic disorders with associated morbidity and mortality. This contribution provides an overview of the diverse rashes associated with potentially lethal, acquired metabolic and endocrine disorders of the pituitary, thyroid, parathyroid, pancreas, adrenals, and blood, as well as neuroendocrine and nutritional disease.


Assuntos
Doenças do Sistema Endócrino/complicações , Exantema/etiologia , Exantema/patologia , Doenças Metabólicas/complicações , Pele/patologia , Humanos , Transtornos Nutricionais/complicações
9.
Postgrad Med ; 132(4): 377-384, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32100608

RESUMO

Globally, osteoarthritis (OA) is the most prevalent arthritic condition in those aged over 60 years. OA has a high impact on patient disability and is associated with a significant economic burden. Pain is the most common first sign of disease and the leading cause of disability. Data demonstrating the increasing global prevalence of OA, together with a greater understanding of the burden of the disease, have led to a reassessment of the seriousness of OA and calls for the designation of OA as a serious disease in line with the diseases impact on comorbidity, disability, and mortality. While OA was traditionally seen as a prototypical 'wear and tear' disease, it is now more accurately thought of as a disease of the whole joint involving cartilage together with subchondral bone and synovium. As more has become known of the pathophysiology of OA, it has become increasingly common for it to be described using a number of overlapping phenotypes. Patients with OA will likely experience multiple phenotypes during their disease. This review focuses on what we feel are three key phenotypes: post-trauma, metabolic, and aging. A greater understanding of OA phenotypes, particularly at the early stages of disease, may be necessary to improve treatment outcomes. In the future, non-pharmacological and pharmacological treatments could be tailored to patients based on the key features of their phenotype and disease pathway.


Assuntos
Envelhecimento/fisiologia , Doenças Metabólicas/complicações , Osteoartrite/etiologia , Osteoartrite/fisiopatologia , Ferimentos e Lesões/complicações , Humanos , Inflamação/fisiopatologia , Artropatias/fisiopatologia , Articulações/lesões , Doenças Metabólicas/fisiopatologia , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Ferimentos e Lesões/fisiopatologia
10.
Curr Opin Pediatr ; 32(2): 284-287, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32068596

RESUMO

PURPOSE OF REVIEW: As the incidence of urinary stone disease in children is increasing, identifying dietary risk factors becomes vitally important, especially in the context of targeting interventions to reduce risk for stone formation. Indiscriminant dietary restrictions are not appropriate for paediatric patients. RECENT FINDINGS: Although large, prospective studies are still needed to better quantify dietary risk factors for paediatric stone formers, a number of smaller studies provide data to identify common risk factors to help prevent stone formation, while minimizing inappropriate dietary restrictions. SUMMARY: Interpretation of 24-h urine samples to identify individualized dietary risk factors is crucial for implementing a strategy for prevention of further urinary stone formation in children. Clinicians should avoid generalized dietary restrictions in stone-forming children uninformed by laboratory data.


Assuntos
Dieta/efeitos adversos , Cálculos Renais/etiologia , Doenças Metabólicas/diagnóstico , Cálculos Urinários/etiologia , Criança , Humanos , Cálculos Renais/metabolismo , Cálculos Renais/urina , Doenças Metabólicas/complicações , Doenças Metabólicas/urina , Fatores de Risco , Fatores Socioeconômicos , Cálculos Urinários/metabolismo , Cálculos Urinários/urina
11.
Adv Exp Med Biol ; 1232: 91-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893399

RESUMO

Vascular cognitive impairment (VCI) plays an important role in dementia in elderly people, and refers to the contribution of vascular pathology to the entire spectrum of cognitive disorders, ranging from mild cognitive impairment to severe dementia, as well as the pathological spectrum, from 'pure' Alzheimer disease through degrees of vascular comorbidity to 'pure' vascular dementia. In the present study, we investigated the relationship between cognitive dysfunction and systemic metabolic disorders, by employing deep learning (DL). We studied 202 patients (73.4 ± 13.0 years), 94.6% of whom were undergoing treatment for lifestyle diseases, and 68.8% of whom had a history of cerebrovascular disorder. We evaluated cognitive dysfunction by performing a Mini Mental State Examination (MMSE). We performed general blood examination, including Complete Blood Count and Basic Metabolic Panel, and measured cerebral blood oxygenation in the prefrontal cortex (PFC) using time-resolved near infrared spectroscopy (TNIRS). We then used deep neural networks to assess the MMSE scores of the subjects based on the TNIRS parameters and the blood examination data, independently. Next, we compared predicted MMSE scores based on the TNIRS and the blood examination. There was a significant positive correlation between the TNIRS parameters and the blood examination data (r = 0.6, p < 0.01). These observations suggest that cognitive dysfunction in patients with VCI may be caused by combinations of systemic metabolic disorders such as energy and oxygen metabolisms and cerebral circulatory disturbance due to arteriosclerosis resulting from lifestyle-related diseases.


Assuntos
Disfunção Cognitiva , Demência , Doenças Metabólicas , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/complicações , Demência/complicações , Demência/fisiopatologia , Feminino , Humanos , Masculino , Doenças Metabólicas/complicações , Pessoa de Meia-Idade
12.
Eur J Pharmacol ; 870: 172913, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31926994

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are considered major global medical burdens with high prevalence and steeply rising incidence. Despite the characterization of numerous pathophysiologic pathways leading to metabolic disorder, lipid accumulation, inflammation, fibrosis, and ultimately end-stage liver disease or liver cancer formation, so far no causal pharmacological therapy is available. Drug development for NAFLD and NASH is limited by long disease duration and slow progression and the need for sequential biopsies to monitor the disease stage. Additional non-invasive biomarkers could therefore improve design and feasibility of such. Here, the current concepts on preclinical models, biomarkers and clinical endpoints and trial designs are briefly reviewed.


Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Biomarcadores , Progressão da Doença , Desenvolvimento de Medicamentos , Fibrose/complicações , Fibrose/tratamento farmacológico , Humanos , Incidência , Inflamação/complicações , Inflamação/tratamento farmacológico , Fígado/metabolismo , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Doenças Metabólicas/complicações , Doenças Metabólicas/tratamento farmacológico , Prevalência , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Int J Mol Sci ; 21(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947993

RESUMO

Acute pancreatitis (AP) is a severe inflammation of the pancreas presented with sudden onset and severe abdominal pain with a high morbidity and mortality rate, if accompanied by severe local and systemic complications. Numerous studies have been published about the pathogenesis of AP; however, the precise mechanism behind this pathology remains unclear. Extensive research conducted over the last decades has demonstrated that the first 24 h after symptom onset are critical for the identification of patients who are at risk of developing complications or death. The identification of these subgroups of patients is crucial in order to start an aggressive approach to prevent mortality. In this sense and to avoid unnecessary overtreatment, thereby reducing the financial implications, the proper identification of mild disease is also important and necessary. A large number of multifactorial scoring systems and biochemical markers are described to predict the severity. Despite recent progress in understanding the pathophysiology of AP, more research is needed to enable a faster and more accurate prediction of severe AP. This review provides an overview of the available multifactorial scoring systems and biochemical markers for predicting severe AP with a special focus on their advantages and limitations.


Assuntos
Biomarcadores/sangue , Pancreatite/diagnóstico , Doença Aguda , Humanos , Interleucinas/sangue , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Pancreatite/diagnóstico por imagem , Pancreatite/metabolismo , Prognóstico , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Fator de Necrose Tumoral alfa/sangue
14.
Int J Mol Sci ; 21(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31948011

RESUMO

Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating meningeal tissues. Many of these nociceptors also contain vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. Release of neuropeptides and other functional properties are frequently examined using the cell bodies of trigeminal neurons as models of their sensory endings. Pathophysiological conditions cause phosphorylation, increased expression and trafficking of transient receptor potential (TRP) channels, neuropeptides and other mediators, which accelerate activation of nociceptive pathways. Since nociceptor activation may be a significant pathophysiological mechanism involved in both peripheral and central sensitization of the trigeminal nociceptive pathway, its contribution to the pathophysiology of primary headaches is more than likely. Metabolic disorders and medication-induced painful states are frequently associated with TRP receptor activation and may increase the risk for primary headaches.


Assuntos
Cefaleia/patologia , Nociceptores/metabolismo , Canais de Receptores Transientes de Potencial/metabolismo , Cálcio/metabolismo , Depressão Alastrante da Atividade Elétrica Cortical , Cefaleia/metabolismo , Humanos , Meninges/metabolismo , Meninges/ultraestrutura , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Neurônios/metabolismo , Neuropeptídeos/metabolismo
15.
Biochem Med (Zagreb) ; 30(1): 010701, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31839721

RESUMO

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition that can affect haemostasis. This study aimed to determine differences in platelet-related parameters between controls and COPD subjects. The hypothesis was that platelet indices are disturbed in COPD patients, and this would be accompanied by increased C-reactive protein (CRP), fibrinogen (Fbg) and white blood cells (WBC). Therefore, platelet count (Plt), platelet-related parameters - mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (Pct), their ratios (MPV/Plt, MPV/Pct, PDW/Plt, PDW/Pct), platelet to lymphocyte ratio (PLR), Plt index as well as CRP, Fbg and WBC were assessed. Materials and methods: Study included 109 patients with stable COPD and 95 control subjects, recruited at Clinical Department for Lung Diseases Jordanovac, University Hospital Centre Zagreb (Zagreb, Croatia). Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. Results: Platelet (P = 0.007) and PLR (P = 0.006) were increased, while other platelet indices were decreased in COPD patients compared to controls. Combined model that included PLR, PDW and WBC showed great diagnostic performances, and correctly classified 75% of cases with an AUC of 0.845 (0.788 - 0.892), P < 0.001. Comorbidities (cardiovascular or metabolic diseases) had no effect on investigated parameters, while inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA) therapy increased MPV and PDW values in COPD patients. Conclusion: Platelet indices were altered in COPD patients and they could be valuable as diagnostic markers of COPD development, especially if combined with already known inflammatory markers.


Assuntos
Biomarcadores/sangue , Plaquetas/citologia , Doença Pulmonar Obstrutiva Crônica/patologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Plaquetas/metabolismo , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Feminino , Volume Expiratório Forçado , Humanos , Leucócitos/citologia , Modelos Logísticos , Linfócitos/citologia , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
16.
Neurology ; 94(6): e575-e582, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31792095

RESUMO

OBJECTIVE: To determine the prevalence of retinal defect in children with infantile spasms (IS) unrelated to treatment with vigabatrin and clarify if specific primary etiologies for IS are associated with retinal defect more than others. METHODS: This was an observational cohort study including 312 patients (176 male, 136 female) with IS who were vigabatrin-naive. Participants ranged from 1.7 to 34.7 months of age (mean 8.8 months). Electroretinograms (ERGs) were performed according to the International Society for Clinical Electrophysiology of Vision. Retinal defect was identified as abnormal if the 30-Hz flicker ERG amplitude was lower than the age-corrected normal 95% prediction interval. The primary etiology for IS, as determined by the treating pediatric neurologist(s), was obtained from patient health records and classified into 1 of 9 etiologic subgroups: (1) genetic disorders alone, (2) genetic-structural disorders, (3) structural-congenital, (4) structural-acquired (perinatal), (5) structural-acquired (postnatal), (6) metabolic disorders, (7) immunologic disorders, (8) infectious, and (9) unknown causes. RESULTS: Fifty-nine of the 312 vigabatrin-naive children (18.9%) showed retinal defect and the prevalence of retinal defect was highest (24.4%) in the structural-acquired (perinatal) subgroup, which included hypoxic-ischemic defect. Retinal function compared across subgroups showed no significant difference. CONCLUSIONS: Care is required in diagnosing retinal toxicity, which would be enhanced by baseline flicker ERG in children with IS prior to starting vigabatrin.


Assuntos
Doenças Retinianas/epidemiologia , Espasmos Infantis/epidemiologia , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Eletrorretinografia , Feminino , Doenças Genéticas Inatas/complicações , Humanos , Hipóxia-Isquemia Encefálica/complicações , Lactente , Infecções/complicações , Masculino , Doenças Metabólicas/complicações , Prevalência , Doenças Retinianas/fisiopatologia , Espasmos Infantis/tratamento farmacológico , Espasmos Infantis/etiologia , Espasmos Infantis/fisiopatologia , Vigabatrina/uso terapêutico
17.
Expert Rev Clin Pharmacol ; 13(1): 23-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794280

RESUMO

Introduction: Dementia is the 7th leading cause of death that imposes a significant financial and service burden on the global population. Presently, only symptomatic care exists for cognitive loss, such as Alzheimer's disease.Areas covered: Given the advancing age of the global population, it becomes imperative to develop innovative therapeutic strategies for cognitive loss. New studies provide insight to the association of cognitive loss with metabolic disorders, such as diabetes mellitus.Expert opinion: Diabetes mellitus is increasing in incidence throughout the world and affects 350 million individuals. Treatment strategies identifying novel pathways that oversee metabolic and neurodegenerative disorders offer exciting prospects to treat dementia. The mechanistic target of rapamycin (mTOR) and circadian clock gene pathways that include AMP activated protein kinase (AMPK), Wnt1 inducible signaling pathway protein 1 (WISP1), erythropoietin (EPO), and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) provide novel strategies to treat cognitive loss that has its basis in metabolic cellular dysfunction. However, these pathways are complex and require precise regulation to maximize treatment efficacy and minimize any potential clinical disability. Further investigations hold great promise to treat both the onset and progression of cognitive loss that is associated with metabolic disease.


Assuntos
Disfunção Cognitiva/etiologia , Complicações do Diabetes/epidemiologia , Doenças Metabólicas/complicações , Animais , Relógios Circadianos/genética , Disfunção Cognitiva/fisiopatologia , Complicações do Diabetes/psicologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Humanos , Serina-Treonina Quinases TOR/metabolismo
18.
Biochim Biophys Acta Mol Basis Dis ; 1866(2): 165414, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30794867

RESUMO

In recent years, the vascular endothelium has gained attention as a key player in the initiation and development of pregnancy disorders. Endothelium acts as an endocrine organ that preserves the homeostatic balance by responding to changes in metabolic status. However, in metabolic disorders, endothelial cells adopt a dysfunctional function, losing their normal responsiveness. During pregnancy, several metabolic changes occur, in which endothelial function decisively participates. Similarly, when pregnancy metabolic disorders occur, endothelial dysfunction plays a key role in pathogenesis. This review outlines the main findings regarding endothelial dysfunction in three main metabolic pathological conditions observed during pregnancy: gestational diabetes, hypertensive disorders, and obesity and hyperlipidemia. Organ, histological and cellular characteristics were thoroughly described. Also, we focused in discussing the underlying molecular mechanisms involved in the cellular signaling pathways that mediate responses in these pathological conditions.


Assuntos
Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Doenças Metabólicas/metabolismo , Complicações na Gravidez/metabolismo , Animais , Diabetes Gestacional/metabolismo , Eclampsia/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/patologia , Feminino , Homeostase , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Hipertensão Induzida pela Gravidez/metabolismo , Lipídeos/sangue , Doenças Metabólicas/complicações , Doenças Metabólicas/genética , Obesidade Materna/complicações , Obesidade Materna/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/patologia , Transdução de Sinais
19.
J Natl Cancer Inst ; 112(1): 78-86, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30918958

RESUMO

BACKGROUND: There are an estimated 1.4 million colorectal cancer (CRC) survivors in the United States. Research on endocrine and metabolic diseases over the long term in CRC survivors is limited. Obesity is a risk factor for CRC; thus it is of interest to investigate diseases that may share this risk factor, such as diabetes, for long-term health outcomes among CRC survivors. METHODS: A total of 7114 CRC patients were identified from the Utah Population Database and matched to a general population cohort of 25 979 individuals on birth year, sex, and birth state. Disease diagnoses (assessed over three time periods of 1-5 years, 5-10 years, and >10 years) were identified using electronic medical records and statewide ambulatory and inpatient discharge data. Cox proportional hazard models were used to estimate the risk of endocrine and metabolic disease. RESULTS: Across all three time periods, risks for endocrine and metabolic diseases were statistically significantly greater for CRC survivors compared with the general population cohort. At 1-5 years postdiagnosis, CRC survivors' risk for diabetes mellitus with complications was statistically significantly elevated (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.09 to 1.70). CRC survivors also experienced a 40% increased risk of obesity at 1-5 years postcancer diagnosis (HR= 1.40, 99% CI= 1.66 to 2.18) and a 50% increased risk at 5-10 years postdiagnosis (HR = 1.50, 99% CI= 1.16 to 1.95). CONCLUSIONS: Endocrine and metabolic diseases were statistically significantly higher in CRC survivors throughout the follow-up periods of 1-5 years, 5-10 years, and more than 10 years postdiagnosis. As the number of CRC survivors increases, understanding the long-term trajectory is critical for improved survivorship care.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/epidemiologia , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Comorbidade , Doenças do Sistema Endócrino/diagnóstico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Doenças Metabólicas/diagnóstico , Vigilância da População , Prognóstico , Sistema de Registros , Fatores de Risco , Programa de SEER , Utah/epidemiologia
20.
Pediatr Clin North Am ; 67(1): 23-43, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31779835

RESUMO

A wide of array of patients with genetic and metabolic conditions present with orthopedic manifestations. This article discusses the most common conditions seen in a typical pediatric orthopedic practice. A few pearls are highlighted for each condition to alert practitioners to some of the pitfalls encountered when treating these often highly challenged children.


Assuntos
Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/etiologia , Acondroplasia/complicações , Criança , Síndrome de Down/complicações , Síndrome de Ehlers-Danlos/complicações , Doenças Genéticas Inatas/complicações , Humanos , Síndrome de Marfan/complicações , Doenças Metabólicas/complicações , Mucopolissacaridoses/complicações , Distrofia Muscular de Duchenne/complicações , Osteocondrodisplasias/complicações , Osteogênese Imperfeita/complicações , Fenótipo , Raquitismo/complicações
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