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1.
Trends Endocrinol Metab ; 35(4): 282-284, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38341338

RESUMO

Maternal hyperglycemia contributes to abnormal fetal development; yet, how it affects fetal metabolism is poorly understood. Perez-Ramirez and colleagues recently provided a comprehensive metabolic atlas of fetal organs isolated from normal and diabetic pregnant mice, identifying novel metabolites and alterations in tissue glucose utilization throughout mid-to-late gestation by maternal hyperglycemia.


Assuntos
Diabetes Gestacional , Hiperglicemia , Feminino , Humanos , Gravidez , Animais , Camundongos , Hiperglicemia/metabolismo , Feto/metabolismo , Glucose/metabolismo , Desenvolvimento Fetal
2.
Free Radic Biol Med ; 154: 105-118, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32387128

RESUMO

Coenzyme Q (CoQ) is an essential player in the respiratory electron transport chain and is the only lipid-soluble antioxidant synthesized endogenously in mammalian and yeast cells. In humans, genetic mutations, pathologies, certain medical treatments, and aging, result in CoQ deficiencies, which are linked to mitochondrial, cardiovascular, and neurodegenerative diseases. The only strategy available for these patients is CoQ supplementation. CoQ supplements benefit a small subset of patients, but the poor solubility of CoQ greatly limits treatment efficacy. Consequently, the efficient delivery of CoQ to the mitochondria and restoration of respiratory function remains a major challenge. A better understanding of CoQ uptake and mitochondrial delivery is crucial to make this molecule a more efficient and effective therapeutic tool. In this study, we investigated the mechanism of CoQ uptake and distribution using the yeast Saccharomyces cerevisiae as a model organism. The addition of exogenous CoQ was tested for the ability to restore growth on non-fermentable medium in several strains that lack CoQ synthesis (coq mutants). Surprisingly, we discovered that the presence of CoQ biosynthetic intermediates impairs assimilation of CoQ into a functional respiratory chain in yeast cells. Moreover, a screen of 40 gene deletions considered to be candidates to prevent exogenous CoQ from rescuing growth of the CoQ-less coq2Δ mutant, identified six novel genes (CDC10, RTS1, RVS161, RVS167, VPS1, and NAT3) as necessary for efficient trafficking of CoQ to mitochondria. The proteins encoded by these genes represent essential steps in the pathways responsible for transport of exogenously supplied CoQ to its functional sites in the cell, and definitively associate CoQ distribution with endocytosis and intracellular vesicular trafficking pathways conserved from yeast to human cells.


Assuntos
Doenças Mitocondriais , Proteínas de Saccharomyces cerevisiae , Animais , Proteínas de Ligação ao GTP , Humanos , Lipídeos , Proteínas dos Microfilamentos , Acetiltransferase N-Terminal B , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Ubiquinona/metabolismo , Proteínas de Transporte Vesicular
4.
Artigo em Inglês | MEDLINE | ID: mdl-27141989

RESUMO

Tubulin is a potent molecular target for development of anticancer agents. In this report, the binding of non-steroidal anti-inflammatory drugs as tubulin inhibitors potential are investigated by extensive computational techniques, such as, molecular docking, molecular dynamics simulations and binding free energy calculations. The results suggest that a potent indomethacin derivative inhibits the tubulin polymerization by interacting on the colchicine-site binding. This potential chemotherapeutic agent showed high stability in the molecular dynamics simulations, when complexed on the same binding site of colchicine, a potent and toxic, tubulin inhibitor. Then, our results can be useful designing new compounds for cancer treatments.


Assuntos
Antineoplásicos/química , Simulação por Computador , Desenho de Fármacos , Indometacina/farmacologia , Moduladores de Tubulina/química , Sítios de Ligação , Colchicina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Polimerização , Termodinâmica
5.
Crit Care Nurs Clin North Am ; 26(2): 263-75, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24878211

RESUMO

Enteral nutrition is an important aspect of caring for critically ill patients, yet delays in implementation of guidelines and recommendations occur. Bedside caregivers are in a key position to evaluate current practice and lead change to implement evidence-based practice guidelines. Interdisciplinary teams can use change models, such as Larrabee's, to provide guidance and support success of practice change projects.


Assuntos
Cuidadores , Cuidados Críticos/métodos , Nutrição Enteral/enfermagem , Cuidadores/psicologia , Estado Terminal/enfermagem , Medicina Baseada em Evidências , Humanos
7.
Clin Nurse Spec ; 27(5): 231-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23942102

RESUMO

PURPOSE/OBJECTIVES: The aims of this study were to determine the feasibility of and test a multicomponent, nonpharmacologic, nurse-driven intervention for prevention of delirium. DESIGN: This was a prospective, cohort pilot study. SETTING: This study was carried out in a 12-bed medical intensive care unit in a Magnet-designated community hospital in a major metropolitan city in the Southwest United States. SAMPLE: A convenience sample of consented patients meeting inclusion criteria was included in this study. METHODS: A multicomponent prevention protocol consisting of sedation cessation, sleep-wake cycles, sensory stimulation, mobility, and music was tested. FINDINGS: Capturing data for the interventions was problematic. Insufficient documentation systems and inadequate multidisciplinary participation in carrying out the protocol, especially mobility, were barriers. CONCLUSIONS: There was little difference in the proportion of delirium before and after intervention. Success in the identification and prevention of delirium requires a multidisciplinary approach. IMPLICATIONS: Further research is needed using a larger sample size. Refinement of a mobility program is needed.


Assuntos
Delírio/prevenção & controle , Unidades de Terapia Intensiva , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Sudoeste dos Estados Unidos
8.
Arq Neuropsiquiatr ; 68(2): 216-23, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20464288

RESUMO

UNLABELLED: Headache is a worldwide health problem which affects quality of life. OBJECTIVE: To identify the prevalence and management of headache and examine its impact. METHOD: A cross-sectional study with 240 participants was performed to collect data related to (a) headache occurrence, (b) its impact through the "Migraine Disability Assessment Test" (Midas), and (c) headache management. RESULTS: Last year prevalence (2008) was 64.6%. There was a low Midas score in 80.6% of cases. With regard to headache management, 86.4% of respondents said that they use medicines, mainly analgesics (73.9%). Prescribed medicines were used in 31.0% of cases, although 72.4% of those were old prescriptions. Headache was associated with gender (p=0.0002), occupation (p=0.0109) and mean age (p=0.0083), while the Midas score was associated with pain intensity (p=0.0069) and the use of drugs only during headache crisis (p=0.0464). CONCLUSION: There was a high prevalence of headaches and a low level of disability among the population studied, being the management based on self-medication.


Assuntos
Cefaleia/epidemiologia , Automedicação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Estudos Transversais , Feminino , Cefaleia/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Fatores Socioeconômicos , Adulto Jovem
9.
Arq. neuropsiquiatr ; 68(2): 216-223, Apr. 2010. tab
Artigo em Inglês | LILACS | ID: lil-545918

RESUMO

Headache is a worldwide health problem which affects quality of life. OBJECTIVE: To identify the prevalence and management of headache and examine its impact. METHOD: A cross-sectional study with 240 participants was performed to collect data related to (a) headache occurrence, (b) its impact through the "Migraine Disability Assessment Test" (Midas), and (c) headache management. RESULTS: Last year prevalence (2008) was 64.6 percent. There was a low Midas score in 80.6 percent of cases. With regard to headache management, 86.4 percent of respondents said that they use medicines, mainly analgesics (73.9 percent). Prescribed medicines were used in 31.0 percent of cases, although 72.4 percent of those were old prescriptions. Headache was associated with gender (p=0.0002), occupation (p=0.0109) and mean age (p=0.0083), while the Midas score was associated with pain intensity (p=0.0069) and the use of drugs only during headache crisis (p=0.0464). CONCLUSION: There was a high prevalence of headaches and a low level of disability among the population studied, being the management based on self-medication.


As cefaléias constituem um problema de saúde mundial que afeta a qualidade de vida. OBJETIVO: Identificar a prevalência de cefaléias, conhecendo seu impacto e manejo adotado. MÉTODO: Estudo transversal com 240 participantes, coletando-se dados relacionados à ocorrência de cefaléia; impacto através do Migraine Disability Assessment Test (Midas); e manejo. RESULTADOS: A prevalência no último ano (2008) foi 64,6 por cento. O escore do Midas foi pequeno em 80,6 por cento dos casos. Em relação ao manejo, 86,4 por cento dos entrevistados utilizavam medicamentos, principalmente, analgésicos (73,9 por cento). Em 31,0 por cento das situações o medicamento foi prescrito, sendo que destas, 72,4 por cento eram prescrições antigas. A cefaléia associou-se com gênero (p=0,0002), situação profissional (p=0,0109) e média de idade (p=0,0083) e o Midas com intensidade da dor (p=0,0069) e uso de medicamentos apenas na crise (p=0,0464). CONCLUSÃO: Houve alta prevalência de cefaléias e baixo grau de inaptidão na população estudada, sendo o manejo baseado na automedicação.


Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Cefaleia/epidemiologia , Automedicação/estatística & dados numéricos , Brasil/epidemiologia , Estudos Transversais , Cefaleia/tratamento farmacológico , Prevalência , Índice de Gravidade de Doença , Fatores Socioeconômicos , Adulto Jovem
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