RESUMO
Planarian Dugesia japonica is a flatworm that can autonomously regenerate its own body after an artificial amputation. A recent report showed the role of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway in the head morphogenesis during the planarian regeneration process after amputation; however, neuron-specific regeneration mechanisms have not yet been reported. Here, whether MEK/ERK pathway was involved in the dopaminergic neuronal regeneration in planarians was investigated. Planarians regenerated their body within 14 days after amputation; however, the head region morphogenesis was inhibited by MEK inhibitor U0126 (3 or 10 µM). Furthermore, the number of planarian tyrosine hydroxylase (DjTH)-positive dopaminergic neurons in the regenerated head region was also decreased by U0126. The 6-hydroxydopamine (6-OHDA), a dopaminergic neurotoxin, can decrease the number of dopaminergic neurons; however, planarians can regenerate dopaminergic neurons after injecting 6-OHDA into the intestinal tract. MEK inhibitor PD98059 (30 µM) or U0126 (10 µM) significantly decreased dopaminergic neurons 5 days after the 6-OHDA injection. During the regeneration process of dopaminergic neurons, phosphorylated histone H3 (H3P)-positive stem cells known as "neoblasts" were increased in the head region; however, MEK inhibitors significantly decreased the number of H3P-positive neoblasts. These results suggested that dopaminergic neuronal regeneration in planarian was regulated by the MEK/ERK pathway.
Assuntos
Planárias , Animais , Dopamina/fisiologia , Neurônios Dopaminérgicos , Quinases de Proteína Quinase Ativadas por Mitógeno , Oxidopamina/toxicidade , Planárias/fisiologiaRESUMO
BACKGROUND: Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. METHODS: This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. RESULTS: Patients' mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan-Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P < 0.05). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (odds ratio, 1.86; 95% confidence interval, 1.08-3.12; P = 0.03). CONCLUSION: SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who underwent CR.
Assuntos
Reabilitação Cardíaca , Produtos Finais de Glicação Avançada/metabolismo , Insuficiência Cardíaca/reabilitação , Pele/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Reabilitação Cardíaca/efeitos adversos , Reabilitação Cardíaca/mortalidade , Causas de Morte , Feminino , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Incidência , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Tóquio/epidemiologiaRESUMO
Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (ß = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.
Assuntos
Reabilitação Cardíaca/métodos , Doenças Cardiovasculares/terapia , Tolerância ao Exercício/fisiologia , Volume Sistólico/fisiologia , Rigidez Vascular/fisiologia , Idoso , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Estudos RetrospectivosRESUMO
BACKGROUND: Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. METHODS: We enrolled 319 consecutive CVD patients aged ≥40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). RESULTS: The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P < 0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P < 0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). CONCLUSION: High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM.
Assuntos
Reabilitação Cardíaca , Doenças Cardiovasculares/terapia , Tolerância ao Exercício , Produtos Finais de Glicação Avançada/metabolismo , Pele/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background and objectives: Exercise can help ease withdrawal symptoms of smokers. However, there is little information about the physiological responses, such as cardiorespiratory and lactate (La) responses, during exercise from light to moderate intensity combined with transdermal nicotine patches (TNPs) in smokers. This study aimed to investigate the effect of TNPs on the cardiorespiratory and La responses during exercise at light to moderate intensity. Materials and Methods: Fourteen young men (8 non-smokers, 6 current smokers) aged 20 to 26 years participated in this study. They performed an incremental graded submaximal exercise test using an electromagnetic cycle ergometer set from 30 to 210 W with (TNP condition) or without a TNP (control condition) in a random order. The TNP was applied to the left arm 8-10 h prior to starting the exercise to achieve the peak level of blood nicotine concentration. Heart rate (HR), rate of perceived exertion (RPE), oxygen consumption (VO2), ventilation (VE), and blood La at rest and during exercise were measured and analyzed. Results: The HR at rest was significantly higher in the TNP condition than in the control condition (TNP; 74.7 ± 13.8 bpm, control; 65.3 ± 10.8 bpm, p < 0.001). There was no interaction (condition × exercise intensity) between any of the variables, and VO2, VE, RPE, and La during exercise were not significantly different between the conditions. However, HR during exercise was 6.7 bpm higher on average in the TNP condition. Conclusions: The HR during exercise was greater at light to moderate intensity with a TNP. Our study results will guide clinicians or health professionals when prescribing exercise programs combined with TNPs for healthy young smokers.
Assuntos
Aptidão Cardiorrespiratória/fisiologia , Exercício Físico/fisiologia , Ácido Láctico/análise , Nicotina/efeitos adversos , Dispositivos para o Abandono do Uso de Tabaco/efeitos adversos , Adulto , Teste de Esforço/métodos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Nicotina/farmacologia , Nicotina/uso terapêutico , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Abandono do Hábito de Fumar/métodos , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Agentes de Cessação do Hábito de Fumar/farmacologia , Agentes de Cessação do Hábito de Fumar/uso terapêuticoRESUMO
BACKGROUND: Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODSâANDâRESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-ß, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. CONCLUSIONS: Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.
Assuntos
Aneurisma da Aorta Abdominal/prevenção & controle , Ácidos Graxos Ômega-3/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/fisiopatologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arginase/genética , Quimiocina CCL2/genética , Inflamação/patologia , Inflamação/fisiopatologia , Inflamação/prevenção & controle , Mediadores da Inflamação/antagonistas & inibidores , Interleucina-6/genética , Transferases Intramoleculares/genética , Transferases Intramoleculares/metabolismo , Lipídeos/sangue , Lipídeos/química , Macrófagos Peritoneais/patologia , Macrófagos Peritoneais/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Objective: Due to the lack of information on the effects of nutritional guidance focused on leucine intake in patients undergoing maintenance cardiac rehabilitation, this study investigated on plasma leucine concentrations, lean body mass, and muscle strength. Methods: Nutritional guidance, focused on leucine (intervention group) or general nutritional guidance (control group), was provided for six months to patients participating in cardiac rehabilitation. Body composition, grip strength, hematological test results, and diet of both groups were compared before and after the intervention. Results: Seven patients in the intervention group (53.2â ±â 18.2 years) and 7 patients in the control group (58.6â ±â 15.3 years) were included. Dietary survey results showed that the six-month intervention significantly (pâ <â 0.05) increased protein intake and estimated leucine intake only in the intervention group. There was no significant difference in the rate of change in plasma leucine concentration between the two groups. The rate of change in lean body mass was significantly higher in the intervention group compared to the control group (pâ =â 0.035). The rate of change in plasma leucine concentration and that in lean body mass was positively correlated only in the intervention group (râ =â 0.777, pâ =â 0.040), and the rate of change in plasma leucine concentration was also positively correlated with the rate of change in grip strength (ρâ =â 0.857, pâ =â 0.014). Conclusions: In the patients undergoing maintenance cardiac rehabilitation, increased plasma leucine concentration by nutritional guidance focused on leucine increased lean body mass without any increasing the training load.
RESUMO
Lactococcus lactis strain Plasma (LC-Plasma) is a unique lactic acid bacterium that activates plasmacytoid dendritic cells (pDCs). We evaluated the effect of LC-Plasma on fatigue indices and dendritic cells activity in athletes after 14 days' continuous exercise load. Thirty-seven participants were divided into two groups and consumed placebo (PL) or LC-Plasma capsules (containing 100 billion cells) daily for 14 days. Maturation markers on dendritic cells, blood parameters, physiological indices, and fatigue-related indices were recorded on days 1 and 15 (before and after exercise). Cumulative days of symptoms relating to physical conditions were also recorded during the continuous exercise period. We observed that CD86 as a maturation marker on pDCs was significantly higher and that cumulative days of fatigue were significantly fewer in the LC-Plasma group than in the Placebo group on day 15. We also conducted 2 h ergometer exercise on day 15 to evaluate fatigue. The results showed that autonomic fatigue parameters (LF/HF) were significantly lower in the LC-Plasma group. These results suggest that LC-Plasma supplementation alleviates fatigue accumulation and increases pDC activity caused by a continuous high training load.
Assuntos
Lactococcus lactis , Humanos , Lactococcus lactis/fisiologia , Temperatura Alta , Células Dendríticas/microbiologia , Fadiga , Exercício Físico , Método Duplo-CegoRESUMO
AIM: Although it is known that advanced age alters skeletal muscle lipid metabolism, the role(s) of polyunsaturated fatty acid-derived metabolites (mostly eicosanoids and docosanoids) in sarcopenia are not clear. We therefore examined the changes in the metabolites of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in the sarcopenic muscle of aged mice. METHODS: We used 6- and 24-month-old male C57BL/6J mice as healthy and sarcopenic muscle models, respectively. Skeletal muscles were removed from the lower limb and subjected to a liquid chromatography-tandem mass spectrometry analysis. RESULTS: The liquid chromatography-tandem mass spectrometry analysis detected distinct changes of metabolites in the muscles of the aged mice. Of the 63 metabolites identified, nine were significantly higher in the sarcopenic muscle of aged mice compared with the healthy muscle of young mice. In particular, prostaglandin E2 , prostaglandin F2a , thromboxane B2 , 5-hydroxyeicosatetraenoic acid, and 15-oxo-eicosatetraenoic acid (arachidonic acid-derived metabolites), 12-hydroxy-eicosapentaenoic acid and 14,15-epoxy-eicosatetraenoic acid (eicosapentaenoic acid-derived metabolites) and 10-hydroxydocosa-hexaenoic acid and 14-hydroxyoctadeca-pentaenoic acid (docosahexaenoic acid-derived metabolites) were significantly higher in aged tissue compared with young tissue (all P < 0.05). CONCLUSIONS: We observed the accumulation of metabolites in the sarcopenic muscle of aged mice. Our results may provide new insights into the pathogenesis and progression of aging- or disease-related sarcopenia. Geriatr Gerontol Int 2023; 23: 297-303.
Assuntos
Sarcopenia , Camundongos , Masculino , Animais , Ácido Eicosapentaenoico/metabolismo , Ácido Araquidônico , Ácidos Docosa-Hexaenoicos , Camundongos Endogâmicos C57BL , Ácidos Graxos Insaturados , Envelhecimento , Músculo Esquelético/metabolismo , ProstaglandinasRESUMO
Biological response of exposure to radon progeny has long been investigated, but there are only few studies in which absorbed doses in lungs of laboratory animals were estimated. The present study is the first attempt to calculate the doses of inhaled radon progeny for mice. For reference, the doses for rats and humans were also computed with the corresponding models. Lung deposition of particles, their clearance, and energy deposition of alpha particles to sensitive tissues were systematically simulated. Absorbed doses to trachea and bronchi, bronchioles and terminal bronchioles, alveolar-interstitial regions, and whole lung were first provided as a function of monodisperse radon progeny particles with an equilibrium equivalent radon concentration of 1 Bq m(-3) (equilibrium factor, 0.4 and unattached fraction, 0.01). Based on the results, absorbed doses were then calculated for (1) a reference mine condition and (2) a condition previously used for animal experiments. It was found that the whole lung doses for mice, rats, and humans were 34.8, 20.7, and 10.7 nGy (Bq m(-3))(-1) h(-1) for the mine condition, respectively, while they were 16.9, 9.9, and 6.5 nGy (Bq m(-3))(-1) h(-1) for the animal experimental condition. In both cases, the values for mice are about 2 times higher than those for rats, and about 3 times higher than those for humans. Comparison of our data on rats and humans with those published in the literature shows an acceptable agreement, suggesting the validity of the present modeling for mice. In the future, a more sophisticated dosimetric study of inhaled radon progeny in mice would be desirable to demonstrate how anatomical, physiological, and environmental parameters can influence absorbed doses.
Assuntos
Pulmão/metabolismo , Modelos Biológicos , Doses de Radiação , Radônio/farmacocinética , Animais , Feminino , Humanos , Inalação , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Tamanho da Partícula , Ratos Long-EvansRESUMO
Objectives: This study aimed to investigate the effects of drinking oxygenated water on oxygen saturation during exercise under normobaric hypoxic conditions. Materials: A randomized placebo-controlled single-blinded trial was performed. Twenty-two healthy adults (16 men and 6 women), with a mean age (standard deviation) of 22.4 (2.73) years, participated in the study. The participants were randomly assigned to one of two groups: an OX group (drinking oxygenated mineral water) and a control group (drinking normal mineral water). Both groups performed walking exercises under normobaric hypoxic conditions. Blood oxygen saturation (SpO2), pulse rate (PR), and walking distance were measured during exercise. Results: SpO2 decreased and PR increased during exercise in both groups. The decrease in SpO2 was smaller and the increase in PR was greater in the OX group compared with those in the control group. No significant difference was found in walking distance between the two groups. Conclusions: Drinking oxygenated water before exercise may inhibit SpO2 reduction under normobaric hypoxic conditions.
RESUMO
BACKGROUND: Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. METHODS: Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. RESULTS: Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). CONCLUSIONS: These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.
Assuntos
Anlodipino/uso terapêutico , Ácido Azetidinocarboxílico/análogos & derivados , Glicemia/metabolismo , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/sangue , Células-Tronco/metabolismo , Adulto , Idoso , Anlodipino/farmacologia , Ácido Azetidinocarboxílico/farmacologia , Ácido Azetidinocarboxílico/uso terapêutico , Glicemia/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Estudos Cross-Over , Di-Hidropiridinas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Células-Tronco/efeitos dos fármacos , Células-Tronco/patologiaRESUMO
BACKGROUND: Peak oxygen uptake (peak VO2 ) and heart rate reserve (HRR) are independent prognostic markers of cardiovascular disease. However, the impact of peak VO2 and HRR on long-term prognosis after off-pump coronary artery bypass grafting (OP-CABG) remains unclear. HYPOTHESIS: To determine the prognostic impact of peak VO2 and HRR in patients after OP-CABG. RESULTS: We enrolled 327 patients (mean age, 65.1 ± 9.3 years; male, 80%) who underwent OP-CABG and participated in early phase II cardiac rehabilitation. All participants underwent cardiopulmonary exercise testing (CPET) at the beginning of such rehabilitation. Overall, 48 (14.6%) patients died during the median follow-up period of 103 months. The non-survivor had significantly lower levels of peak VO2 (10.6 ± 0.5 vs. 13.7 ± 0.2 ml/kg/min, p < .01) and HRR (24.2 ± 1.8 vs. 32.7 ± 0.8 beats/min, p < .01) than the survivor. In both groups, peak VO2 significantly correlated with HRR (p < .01). Moreover, patients were divided into four groups according to the peak VO2 and HRR levels for predicting total mortality. The low-peak VO2 /low-HRR group had a significantly higher mortality risk than the other groups (hazards ratio, 5.61; 95% confidence interval, 2.59-12.16; p < .01). After adjusted the confounding factors, peak VO2 and HRR were independently associated with total mortality (both p < .05). CONCLUSIONS: HRR is a simple parameter of CPET and an important prognostic marker for the risk stratification of total mortality even in patients with low-peak VO2 after OP-CABG.
Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Teste de Esforço , Idoso , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Feminino , Frequência Cardíaca , Humanos , Masculino , Oxigênio , PrognósticoRESUMO
BACKGROUND: Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on alpha-glucosidase inhibitors (alpha-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of alpha-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear. METHODS AND RESULTS: The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P<0.01). GLP-1 levels were significantly higher at 120 min (P<0.05) and GIP levels were significantly lower at 30 min and 60 min (P<0.05) in the miglitol group compared to other treatments. The reactive hyperemia duration at 120 min was significantly maintained in the miglitol group compared to the other groups. CONCLUSIONS: A single administration of miglitol significantly improved post-prandial glucose/lipid metabolism, incretin secretion, and endothelial dysfunction in diabetic patients with CAD, suggesting that miglitol may be a useful anti-atherogenic agent (UMIN000002264).
Assuntos
1-Desoxinojirimicina/análogos & derivados , Doença das Coronárias/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Endotélio Vascular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases , Incretinas/metabolismo , 1-Desoxinojirimicina/administração & dosagem , Idoso , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/etiologia , Doença das Coronárias/etiologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Endotélio Vascular/fisiopatologia , Inibidores Enzimáticos/administração & dosagem , Feminino , Glucose/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Inositol/administração & dosagem , Inositol/análogos & derivados , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Cardiac rehabilitation (CR) has numerous benefits, including reduction of mortality and cardiovascular events, in patients with coronary artery disease (CAD). However, the long-term effect of phase III CR in elderly patients with stable CAD is still unknown. METHODS AND RESULTS: The 111 elderly male CAD patients (>or=65 years), including 37 subjects participating in supervised CR for 6 months and 74 age-matched controls, were analyzed. The patients were followed for up to 3,500 days, until the occurrence of death or 1 of the following major adverse cardiovascular events (MACE): cardiovascular death, acute coronary syndrome, refractory angina requiring revascularization, admission for congestive heart failure, or stroke. All-cause mortality tended to be lower in the CR group than in the Control group (14% vs 28%, P=0.081). The MACE incidence was significantly lower in the CR group than in the Control group (30% vs 62%, P=0.001). Multivariate Cox proportional hazard analysis showed that the MACE incidence was significantly lower in the CR group than in the Control group [adjusted hazard ratio 0.43 (95% confidence interval 0.20-0.91), P=0.027]. CONCLUSIONS: Phase III CR has the beneficial effect of reducing cardiovascular events even in elderly patients with stable CAD.
Assuntos
Síndrome Coronariana Aguda/epidemiologia , Doença da Artéria Coronariana/reabilitação , Dieta , Terapia por Exercício , Insuficiência Cardíaca/epidemiologia , Educação de Pacientes como Assunto , Acidente Vascular Cerebral/epidemiologia , Síndrome Coronariana Aguda/mortalidade , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Doença da Artéria Coronariana/sangue , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Japão , Lipídeos/sangue , Masculino , Modelos de Riscos Proporcionais , Acidente Vascular Cerebral/mortalidade , Resultado do TratamentoRESUMO
AIM: We examined the changes in oxidative stress, mitochondrial function and muscle atrophy during aging in mice. METHODS: We used 6-, 12- and 24-month (6 M, 12 M and 24 M)-old C57BL/6J mice. Skeletal muscles were removed from the lower limb and used for quantitative real-time polymerase chain reaction, immunoblotting and histological analyses. RESULTS: The muscle weight and myocyte cross-sectional area were significantly decreased in the 12 M and 24 M mice compared with those of the 6 M mice. The levels of the oxidative stress markers, nicotinamide adenine dinucleotide phosphate oxidase 2, nicotinamide adenine dinucleotide phosphate oxidase 4, mitochondrial 4-hydroxy-2-nonenal and 3-nitrotyrosine, were significantly higher in the 24 M mice compared with those of the 6 M mice. Furthermore, the 24 M mice had lower levels of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1 (PGC)-α, peroxisome proliferator-activated receptor gamma coactivator-1ß, sirtuin-1, adenosine triphosphate synthase mitochondria F1 complex α subunit 1 and mitochondrial cytochrome c oxidase 1. The ubiquitin-proteasome pathway genes muscle ring finger-1 and atrogin-1 were significantly upregulated in the 12 M and 24 M mice, and protein synthesis markers (phosphorylated-Akt and -p70 ribosomal S6 kinase) were significantly lower in the 24 M mice compared with the 6 M mice (all P < 0.05). CONCLUSIONS: These findings have important implications for the mechanisms that underlie sarcopenia and frailty processes. Geriatr Gerontol Int 2020; 20: 78-84.
Assuntos
Envelhecimento/metabolismo , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Estresse Oxidativo/genética , Envelhecimento/genética , Animais , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/enzimologia , Mitocôndrias/genética , Células Musculares/citologia , Células Musculares/metabolismo , Atrofia Muscular/genética , Estresse Oxidativo/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1ß, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.
RESUMO
AIM: The Kihon Checklist is a useful screening tool for assessing frailty in older individuals. However, the clinical significance of the Kihon Checklist in cardiac rehabilitation patients remains unclear. The present study aimed to evaluate the relationship between the Kihon Checklist and the clinical parameters in patients who participated in cardiac rehabilitation. METHODS: We enrolled 845 consecutive patients (584 men, mean age 71 years) who participated in cardiac rehabilitation at Juntendo University Hospital, Tokyo, Japan, between November 2015 and October 2017. The patients were divided into non-frailty (n = 287), pre-frailty (n = 270) and frailty (n = 288) groups according to their Kihon Checklist scores. Cardiopulmonary exercise testing was carried out in 302 patients. RESULTS: The frailty group was older and had a higher prevalence of history of heart failure than the non-frailty group, although left ventricular ejection fraction did not differ significantly between groups. Nutritional index, trunk and limb muscle mass, lean body weight, and grip strength were significantly lower in the frailty and pre-frailty groups than those in the non-frailty group. In the cardiopulmonary exercise test, a stepwise significant decrease in peak oxygen uptake was observed across the three groups (non-frailty 17.2 ± 3.6, pre-frailty 16.0 ± 3.4, frailty 14.4 ± 3.5 mL/kg/min, P < 0.01). Multivariate regression analyses showed that the Kihon Checklist score was significantly and independently associated with peak oxygen uptake (r = -0.34, P < 0.0001). CONCLUSIONS: The Kihon Checklist, which was associated with frailty and exercise tolerance, could be used as a clinical assessment method for patients who participated in cardiac rehabilitation. Geriatr Gerontol Int 2019; 19: 287-292.
Assuntos
Reabilitação Cardíaca , Lista de Checagem , Tolerância ao Exercício , Fragilidade , Avaliação Geriátrica/métodos , Consumo de Oxigênio , Atividades Cotidianas , Idoso , Reabilitação Cardíaca/métodos , Reabilitação Cardíaca/estatística & dados numéricos , Lista de Checagem/métodos , Lista de Checagem/normas , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Fragilidade/reabilitação , Humanos , Japão/epidemiologia , Masculino , PrevalênciaRESUMO
BACKGROUND: Lactococcus lactis JCM 5805 (LC-Plasma) is a unique lactic acid bacteria (LAB) which activates plasmacytoid dendritic cells (pDC). We aimed to evaluate the effect of LC-Plasma on dendritic cell (DC) activity and subjective indices of upper respiratory tract infections (URTI) and fatigue in athletes under high intensity exercise. METHODS: We conducted a randomized, placebo-controlled, double-blinded trial. Fifty-one male subjects belonging to a university sports club were randomized into placebo (n = 25) and LC-Plasma (n = 26) groups. Individuals ingested placebo capsules containing cornstarch or LC-Plasma capsules containing 100 billion cells of heat-killed LC-Plasma per day for 13 days. During the intervention period, subjects performed high intensity exercise according to their sports club training regime. Blood and saliva sampling were obtained at days 1 and 14, and physical conditions were recorded in a diary. We investigated expression of maturation markers on DCs, muscle damage and stress markers and used student's t test adjusted by Bonferoni's method for multiple comparison between groups. These data were presented as mean ± SD. We also investigated cumulative days of symptoms regarding infections and fatigue and used Chi-square test for comparison between groups. These data were presented as cumulative number. RESULTS: CD86 as maturation marker on pDC was significantly increased in the LC-Plasma group at day 14 (Placebo: 296 ± 70 vs. LC-Plasma: 365 ± 115; Mean Fluorescent Intensity; p = 0.013). Cumulative days of URTI were significantly lower in the LC-Plasma group (Placebo: URTI positive 56, URTI negative 256 vs. LC-Plasma: URTI positive 39, URTI negative 299; days; p = 0.028) and symptoms like sneeze or running nose were significantly lower in the LC-Plasma group (Placebo: Symptom positive 52, Symptom negative 258, vs. LC-Plasma: Symptom positive 36, Symptom negative 301; days; p = 0.032). Moreover, the cumulative days of fatigue were significantly fewer in the LC-Plasma group (Placebo: Symptom positive 128, Symptom negative 182, vs. LC-Plasma: Symptom positive 110, Symptom negative 225; days; p = 0.032). Markers of muscle damage and stress markers were not significantly different between groups. CONCLUSION: We consider that heat-killed LC-Plasma supplementation relieves morbidity and symptoms of URTI via activation of pDC and decreases fatigue accumulation during consecutive high intensity exercise in athletes. However, LC-Plasma ingestion did not affect markers of muscle damage and stress. TRIAL REGISTRATION: UMIN-CTR, UMIN000020372 . Registered 28 December 2015.