RESUMO
Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.
Assuntos
Parada Cardíaca , Humanos , Camundongos , Animais , Parada Cardíaca/complicações , Quimiocinas , Quimiocinas CCRESUMO
BACKGROUND: The absence of the pupillary light reflex (PLR) 3 days after cardiac arrest predicts poor outcome, but quantitative PLR assessment with pupillometry early after recovery of spontaneous circulation (ROSC) and throughout targeted temperature management (TTM) has rarely been evaluated. METHODS: Fifty-five adult patients treated with TTM with available pupillometry data from the NeurOptics NPi-200 were studied. Discharge outcome was classified good if the cerebral performance category score was 1-2, poor if 3-5. Pupil size, PLR percent constriction (%PLR), and constriction velocity (CV) were determined at TTM start and 6 (± 2)-h post-ROSC ("early"), and throughout TTM using data from the worst eye at each assessment. The Neurological Pupil index (NPi) was also determined at each pupil assessment; the NPi is scored from 0 (nonreactive) to 5 (brisk) with values < 3 considered sluggish or abnormal. Prognostic performance to predict poor outcome was assessed with receiver operator characteristic curves. RESULTS: All nine patients with ≥ 1 nonreactive pupil (NPi = 0) within 6 (± 2) h after ROSC died, and 12/14 (86%) with sluggish pupils (0 < NPi < 3) had poor outcomes. 15/29 (52%) patients with normal pupil reactivity (NPi ≥ 3) had poor outcomes, four survived with cerebral performance category = 3, three died of cardiac causes, and eight died of neurologic causes. During TTM, 20/21 (95%) patients with nonreactive pupils had poor outcomes, 9/14 (64%) of patients with sluggish pupils had poor outcomes, and 9/20 (45%) with normal pupil reactivity had poor outcomes. Pupil size did not predict outcome, but NPi (AUC = 0.72 [0.59-0.86], p < 0.001), %PLR (AUC = 0.75 [0.62-0.88], p < 0.001) and CV (AUC = 0.78 [0.66-0.91], p < 0.001) at 6 h predicted poor outcome. When nonreactive pupils were first detected, 75% were < 5 mm. CONCLUSIONS: Very early after resuscitation from cardiac arrest, abnormal Neurological Pupil index and pupillary light reflex measurements by pupillometer are predictive of poor outcome, and are not usually associated with dilated pupils.
Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca/terapia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/fisiopatologia , Reflexo Anormal/fisiologia , Reflexo Pupilar/fisiologia , Retorno da Circulação Espontânea , Idoso , Técnicas de Diagnóstico Neurológico , Feminino , Parada Cardíaca/complicações , Mortalidade Hospitalar , Humanos , Hipóxia-Isquemia Encefálica/etiologia , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/complicações , Parada Cardíaca Extra-Hospitalar/terapia , PrognósticoRESUMO
OBJECTIVE: SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity. METHODS: Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA. These concentrations were compared to healthy control plasma that is commercially available and was biobanked prior to the start of the pandemic. Additionally, outcomes such as WHO ordinal scale for disease severity, ICU admission, needed for invasive ventilation, hospital length of stay, and development of thrombosis during admission were used as markers of disease severity. RESULTS: Our results show that both CD73 and ADA are decreased during SARS-CoV-2 infection. The level of circulating CD73 is directly correlated to the severity of the disease defined by the need for ICU admission, invasive ventilation, and hospital length of stay. Low level of CD73 is also associated with clinical thrombosis, a severe complication of SARS-CoV-2 infection. CONCLUSION: Our study indicates that adenosine metabolism is down-regulated in patients with COVID-19 and associated with severe infection. Further large-scale studies are warranted to investigate the role of the adenosinergic anti-inflammatory CD73/ADA axis in protection against COVID-19.
Assuntos
COVID-19 , Humanos , Adenosina Desaminase/metabolismo , SARS-CoV-2 , Projetos Piloto , Adenosina/metabolismo , Gravidade do PacienteRESUMO
Aim: Describe community consultation and surrogate consent rates for two Exception From Informed Consent (EFIC) trials for out-of-hospital cardiac arrest (OOHCA) - before and during the COVID-19 pandemic. Methods: The PEARL study (2016-2018) randomized OOHCA patients without ST-elevation to early cardiac catheterization or not. Community consultation included flyers, radio announcements, newspaper advertisements, mailings, and in-person surveys at basketball games and ED waiting rooms. The PROTECT trial (2021-present) randomizes OOHCA survivors to prophylactic ceftriaxone or placebo; the community consultation plan during the pandemic included city council presentations, social media posts, outpatient flyers, but no in-person encounters. Demographics for PROTECT community consultation were compared to PEARL and INTCAR registry data, with p-value < 0.05 considered significant. Results: PEARL surveyed 1,362 adults, including 64 % ≥60 years old, 96 % high school graduates or beyond; research acceptance rate was 92 % for the community and 76 % for personal level. PROTECT initially obtained 221 surveys from electronic media - including fewer males (28 % vs 72 %,p < 0.001) and those > 60 years old (14 % vs 53 %;p < 0.001) compared to INTCAR. These differences prompted a revised community consultation plan, targeting 79 adult in-patients with cardiac disease which better matched PEARL and INTCAR data: the majority were ≥ 60 years old (66 %) and male (54 %). Both PEARL and PROTECT enrolled more patients using surrogate consent vs EFIC (57 %, 61 %), including 71 % as remote electronic consents during PROTECT. Conclusions: Community consultation for EFIC studies changed with the COVID-19 pandemic, resulting in different demographic patterns. We describe effective adaptations to community consultation and surrogate consent during the pandemic.
RESUMO
BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.
Assuntos
Parada Cardíaca Extra-Hospitalar , Pneumonia , Ceftriaxona/efeitos adversos , Método Duplo-Cego , Humanos , Inflamação , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Effectiveness of cooling and adverse events (AEs) involving skin have not been intensively evaluated in cardiac arrest survivors treated with therapeutic hypothermia (TH) when induced and maintained with a servomechanism-regulated surface cooling system. METHODS: Retrospective review of sixty-nine cardiac arrest survivor-events admitted from April 2006-September 2008 who underwent TH using the Medivance Arctic Sun Temperature Management System. A TH database and medical records were reviewed, and nursing interviews conducted. Primary endpoint was time from initiation to target temperature (TT; 32-34 °C). Secondary endpoints were cooling rate, percentage of hypothermia maintenance phase at TT, effect of body-mass index (BMI) on rate of cooling, and AEs. RESULTS: Mean time to the target temperature (TT) was 2.78 h; 80% of patients achieved TT within 4 h; all did within 8 h. Patients were at TT for 96.7% of hypothermia maintenance; 17% of patients had >1 hourly temperature measurement outside TT range. Mean cooling rate during induction phase was 1.1 °C/h, and was not associated with BMI. Minor skin injury occurred in 14 (20%) patients; 4 (6%) were device-related. Skin injuries were associated with shock (P = 0.04), and decubitus ulcers were associated with left ventricular ejection fraction <45% (P = 0.004). AEs included shivering (94%), hypokalemia (81%), hyperglycemia (57%), pneumonia (23%), bleeding (22%), post-cooling fever (17%), and bacteremia (9%). CONCLUSIONS: The Arctic Sun Temperature Management System was an effective means of performing therapeutic hypothermia after cardiac arrest. Infrequent skin injuries were associated with vasopressor use and low ejection fraction.
Assuntos
Parada Cardíaca/terapia , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/instrumentação , Pele/lesões , Idoso , Índice de Massa Corporal , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Humanos , Hipotermia Induzida/enfermagem , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19. Following informed consent, we collected blood samples from hospitalized patients with COVID-19 within 72 h of admission. Flow cytometry was used to analyze white blood cell subpopulations. Plasma levels of cytokines and chemokines were measured using ELISA. Neutrophils undergoing neutrophil extracellular traps (NET) formation were evaluated in blood smears. We examined the immunophenotype of patients with COVID-19 in comparison to that of SARS-CoV-2 negative controls. A novel subset of pro-inflammatory neutrophils expressing a high level of dual endothelin-1 and VEGF signal peptide-activated receptor (DEspR) at the cell surface was found to be associated with elevated circulating CCL23, increased NETosis, and critical-severity COVID-19 illness. The potential to target this subpopulation of neutrophils to reduce secondary tissue damage caused by SARS-CoV-2 infection warrants further investigation.
Assuntos
COVID-19/imunologia , Neutrófilos/imunologia , Pseudogenes/imunologia , Idoso , Quimiocinas/metabolismo , Estudos de Coortes , Estado Terminal , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Armadilhas Extracelulares/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Pseudogenes/genética , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de DoençaRESUMO
Background Patients resuscitated from cardiac arrest ( CA ) have highly variable neurological, circulatory, and systemic ischemia-reperfusion injuries. After the initial hypoxic-ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors. Methods and Results After informed consent, we collected blood samples at intervals over a week after resuscitation from CA . We examined the expression of CD 39 and CD 73 (alias 5'-nucleotidase), production of tumor necrosis factor-α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD 73-expressing lymphocytes correlated with survival after CA . Incubation of immune cells, obtained from post- CA subjects, with AMP , a substrate for CD 73, resulted in inhibition of tumor necrosis factor-α production and generation of reactive oxygen species. This effect was blocked by adenosine 5'-(α, ß-methylene) diphosphate, a specific inhibitor of CD 73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP -dependent activation of CD 73 induces production of vascular endothelial growth factor. Conclusions CD 73-expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD 73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study.
Assuntos
Parada Cardíaca/imunologia , Linfócitos/imunologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/efeitos dos fármacos , 5'-Nucleotidase/imunologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Difosfato de Adenosina/análogos & derivados , Difosfato de Adenosina/farmacologia , Monofosfato de Adenosina/farmacologia , Idoso , Antígenos CD/imunologia , Apirase/imunologia , Reanimação Cardiopulmonar , Estudos de Casos e Controles , Inibidores Enzimáticos/farmacologia , Feminino , Parada Cardíaca/metabolismo , Parada Cardíaca/terapia , Humanos , Técnicas In Vitro , Contagem de Leucócitos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Células Mieloides/imunologia , Células Mieloides/metabolismo , Prognóstico , Triazinas/farmacologia , Triazóis/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate whether 6 months of exercise combined with isoflavone supplementation could improve clinical risk factors that predispose to cardiovascular disease in obese postmenopausal women. DESIGN: This was a randomized, double-blind, controlled trial in which 50 healthy obese postmenopausal women were divided into two groups and assigned to isoflavone supplementation (n=25) or a placebo (n=25) for 1 year. For the last 6 months, both groups participated in an exercise program (three times per week), at the end of which cardiovascular disease risk factors were compared between groups. Body composition (using dual-energy x-ray absorptiometry), metabolic profile (blood lipids, fasting insulin, fasting glucose, sex hormone-binding globulin, C-reactive protein) were determined at baseline and at 6 and 12 months. RESULTS: We observed a significant effect of exercise and isoflavone supplementation on body weight, total and abdominal fat mass (kilograms and percentage), body mass index, appendicular fat-free mass, fat-free mass/fat mass ratio, and sex hormone-binding globulin, but not with exercise alone. No difference was observed for other biochemical characteristics, although the quantitative insulin sensitivity check index increased equally in both groups. Conversely, although not significant, we observed a tendency for a treatment effect on body mass index (P=0.07) and on absolute (kilograms) (P=0.07) and percentage of (P=0.053) abdominal fat mass, whereas no effect of treatment was found for other variables using the Mann-Whitney test. CONCLUSIONS: Compared to an aerobic exercise program alone, 70 mg/day of isoflavones combined with exercise may promote significant improvements in body composition parameters that are known to influence cardiovascular disease risk in postmenopausal women.
Assuntos
Exercício Físico , Glycine max , Isoflavonas/administração & dosagem , Obesidade/terapia , Fitoterapia , Idoso , Glicemia , Composição Corporal , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Insulina/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Pós-Menopausa , Fatores de Risco , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
The postresuscitation period after a cardiac arrest is characterized by a wide range of physiological derangements. Variations between patients include preexisting medical problems, the underlying cause of the cardiac arrest, presence or absence of hemodynamic and circulatory instability, severity of the ischemia-reperfusion injury, and resuscitation-related injuries such as pulmonary aspiration and rib or sternal fractures. Although protocols can be applied to many elements of postresuscitation care, the widely disparate clinical condition of cardiac arrest survivors requires an individualized approach that stratifies patients according to their clinical profile and targets specific treatments to patients most likely to benefit. This article describes such an individualized approach, provides a practical framework for evaluation and triage at the bedside, and reviews concerns specific to all members of the interprofessional postresuscitation care team.
Assuntos
Reanimação Cardiopulmonar/métodos , Cuidados Críticos/métodos , Parada Cardíaca/terapia , Adulto , Idoso , Eletrocardiografia , Eletroencefalografia , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. METHODS AND MATERIALS: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. RESULTS: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). CONCLUSIONS: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.
Assuntos
Neoplasias/diagnóstico , Neoplasias/radioterapia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Ecrans Intensificadores para Raios X , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Loss-of-function mutations affecting the cholesterol transporter ATP-binding cassette transporter subfamily A member 1 (ABCA1) impair cellular cholesterol efflux and are associated with reduced HDL-cholesterol (HDL-C) levels. ABCA1 may also be important in regulating ß-cell cholesterol homeostasis and insulin secretion. We sought to determine whether loss-of-function ABCA1 mutations affect ß-cell secretory capacity in humans by performing glucose-potentiated arginine tests in three subjects homozygous for ABCA1 mutations (age 25 ± 11 years), eight heterozygous subjects (28 ± 7 years), and eight normal control subjects pair-matched to the heterozygous carriers. To account for any effect of low HDL-C on insulin secretion, we studied nine subjects with isolated low HDL-C with no ABCA1 mutations (age 26 ± 6 years) and nine pair-matched control subjects. Homozygotes for ABCA1 mutations exhibited enhanced oral glucose tolerance and dramatically increased ß-cell secretory capacity that was also greater in ABCA1 heterozygous subjects than in control subjects, with no differences in insulin sensitivity. Isolated low HDL-C subjects also demonstrated an increase in ß-cell secretory capacity but in contrast to those with ABCA1 mutations, exhibited impaired insulin sensitivity, supporting ß-cell compensation for increased insulin demand. These data indicate that loss-of-function mutations in ABCA1 in young adults may be associated with enhanced ß-cell secretory capacity and normal insulin sensitivity and support the importance of cellular cholesterol homeostasis in regulating ß-cell insulin secretion.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Colesterol/metabolismo , Resistência à Insulina/fisiologia , Células Secretoras de Insulina/metabolismo , Adolescente , Adulto , Glicemia/metabolismo , Feminino , Intolerância à Glucose/genética , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Heterozigoto , Homeostase/fisiologia , Homozigoto , Humanos , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Masculino , Mutação , Adulto JovemRESUMO
The aim of this study was to establish a cut-off value of percentage of fat mass (%FM) at which insulin sensitivity (IS) is significantly altered in sedentary postmenopausal women. Our results suggest that maintaining a %FM below 41% would minimize the deterioration of IS and its associated risks.
Assuntos
Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Resistência à Insulina/fisiologia , Insulina/metabolismo , Pós-Menopausa/metabolismo , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal/fisiologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
AIMS: To investigate whether 6 months of isoflavone supplementation, which has been shown to be sufficient to improve menopausal symptoms, could also improve clinical cardiovascular disease (CVD) risk factors in obese postmenopausal women, compared with a placebo. METHODS: A randomized double-blind placebo-controlled trial in which 50 obese postmenopausal women were divided into two groups (isoflavones vs. placebo) to examine the effect of 6 months of isoflavone supplement (70 mg) on clinical CVD risk factors. Body composition (DXA), medical and social characteristics, daily energy expenditure (accelerometry), dietary intake (3-day dietary record), and blood biochemical analyses (lipid profile, insulin, glucose) were obtained. RESULTS: At baseline, no differences were found between groups except for fasting insulin level. Women were thus considered at risk of CVD based on body composition but not biochemical variables. After 6 months, we observed that isoflavones did not favorably affect risk factors predisposing to CVD (biochemical or body composition) compared with placebo. CONCLUSIONS: Isoflavones given for 6 months should not be considered protective against clinical CVD risk factors in obese postmenopausal women. Nevertheless, further research is needed to verify if isoflavones protect against CVD disease risk factors when administered for a longer duration or when combined with nutritional or exercise interventions. It would also be pertinent to study their effects in women with specific metabolic abnormalities.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Isoflavonas/administração & dosagem , Lipídeos/sangue , Idoso , Glicemia , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Insulina/sangue , Pessoa de Meia-Idade , Obesidade/complicações , Projetos Piloto , Placebos , Pós-Menopausa , Fatores de RiscoRESUMO
It is known that obesity is inversely correlated with fracture risk. It remains unclear if a low muscle mass (sarcopenia) modulates the relationship between obesity and bone mass density. Twenty-seven obese women were matched for total fat mass (+/- 0.5 kg) and age (+/- 4 yrs) and divided in 3 equal groups: class II sarcopenic, class I sarcopenic, and nonsarcopenic. Body composition (DXA) and dietary intake were measured. Our results suggest that obesity may offer some protection against osteoporosis, even in sarcopenic postmenopausal women. However, further studies are needed to examine the actual implication of these results on a clinical standpoint.
Assuntos
Fraturas Ósseas/complicações , Fraturas Ósseas/prevenção & controle , Atrofia Muscular/complicações , Atrofia Muscular/fisiopatologia , Obesidade/complicações , Pós-Menopausa , Absorciometria de Fóton , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Saúde da MulherRESUMO
Insulin plays a pivotal role in skeletal muscle protein metabolism and its action decreases with age. A loss of muscle mass, termed sarcopenia, also occurs with age. The age-associated decline in insulin sensitivity (IS) may negatively alter muscle protein metabolism and, therefore, be implicated in the aetiology of sarcopenia. However, no studies have yet compared the level of IS between older individuals with or without sarcopenia. Thus, in this study, we compared the IS of 20 class I sarcopenics (CIS), 8 class II sarcopeniscs (CIIS), and 16 non-sarcopenics (NS), among a group of otherwise healthy, non-obese, postmenopausal women. IS was estimated with the quantitative IS check index (QUICKI). Muscle mass index (MMI), which was used to determine sarcopenia, was calculated as follows: (appendicular muscle massx1.19)-1.01/h2, where h=height. Fat-free mass (FFM), fat mass (FM), and trunk FM (TFM) were measured by dual-energy X-ray absorptiometry. Accelerometry and indirect calorimetry were used to estimate resting (REE), daily (DEE), and physical activity (PAEE) energy expenditure. A 3 d food record was used to determine total energy, protein (animal and vegetal), and carbohydrate intakes. As expected, MMI and FFM differed significantly among groups. However, no significant differences were found among groups for IS, FM, TFM, REE, DEE, PAEE, or total energy, protein (both animal and vegetable), and carbohydrate intakes. Using QUICKI, a surrogate measure of IS, the present results suggest that the action of insulin does not play an important role in the development and maintenance of sarcopenia in healthy, non-obese, postmenopausal women.
Assuntos
Envelhecimento/fisiologia , Resistência à Insulina , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Pós-Menopausa/fisiologia , Composição Corporal , Índice de Massa Corporal , Metabolismo Energético , Feminino , Humanos , Projetos Piloto , Análise de RegressãoRESUMO
BACKGROUND AND AIM: No study to date has documented the association between short sleep duration and the risk for obesity in older people. Therefore, the aim of this study was to examine cross-sectional associations between short sleep duration and variations in body fat indices in older women. METHODS: Anthropometric and body composition measurements, resting energy expenditure, daily energy expenditure, daily energy intake, plasma lipid-lipoprotein profile, and self-reported sleep duration were determined in a sample of 90 women of 50 years and above. RESULTS: The odds ratios for overweight/obesity were comparable in subjects reporting <7 hours and >or=7 hours of sleep per day, with or without adjustment for age, daily energy expenditure and daily energy intake. The results did not permit to observe any significant difference between the two sleeper groups for all the variables investigated. The correlations between sleep duration and adiposity indices were also non significant. CONCLUSIONS: Short sleep duration does not predict an increased risk of being overweight/obese in older women. This observation, together with our previously reported results in younger subjects, suggests that the sleep-body fat relationship progressively becomes less detectable with increasing in age.
Assuntos
Envelhecimento/fisiologia , Obesidade/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Sono/fisiologia , Idoso , Composição Corporal/efeitos dos fármacos , Estudos Transversais , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Feminino , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Razão de Chances , Fatores de Risco , Transtornos do Sono-Vigília/fisiopatologia , Leite de Soja/farmacologia , Fatores de TempoRESUMO
OBJECTIVE: To compare sarcopenic-obese and obese postmenopausal women for risk factors predisposing to cardiovascular disease (CVD) and determine whether there may be a relationship between muscle mass and metabolic risk in obese postmenopausal women. RESEARCH METHODS AND PROCEDURES: In this cross-sectional study, 22 healthy obese postmenopausal women (mean age, 66 +/- 5 years; mean BMI, 27 +/- 3 kg/m(2)) were divided into two groups matched for age (+/-2 years) and fat mass (FM) (+/-2%). Sarcopenia was defined as a muscle mass index of <14.30 kg fat-free mass (FFM)/m(2) (which corresponds to 1 standard deviation below the values of a young reference population), and obesity was defined as an FM of >35% (which corresponds to the World Health Organization guidelines). FM, FFM (measured by DXA), daily energy expenditure (accelerometry), dietary intake (3-day dietary record), and blood biochemical analyses (lipid profile, insulin, glucose, and C-reactive protein) were obtained. Visceral fat mass (VFM) was calculated by the equation of Bertin, which estimates VFM from DXA measurements. RESULTS: Obese women had more FFM (p = 0.006), abdominal FM (p = 0.047), and VFM (p = 0.041) and a worse lipid profile [p = 0.040 for triglycerides; p = 0.004 for high-density lipoprotein (HDL); p = 0.026 for total cholesterol/HDL] than sarcopenic-obese postmenopausal women. Obese women also ingested significantly more animal (p = 0.001) and less vegetal proteins (p = 0.013), although both groups had a similar total protein intake (p = 0.967). DISCUSSION: Sarcopenia seems to be associated with lower risk factors predisposing to CVD in obese postmenopausal women. With the increase in the number of aging people, the health implications of being sarcopenic-obese merit more attention.