RESUMO
Higher intensity exercise, despite causing more tissue damage, improved aging conditions. We previously observed decreased p16INK4a mRNA in human skeletal muscle after high-intensity interval exercise (HIIE), with no change following equivalent work in moderate-intensity continuous exercise. This raises the question of whether the observed senolytic effect of exercise is mediated by inflammation, an immune response induced by muscle damage. In this study, inflammation was blocked using a multiple dose of ibuprofen (total dose: 1200 mg), a commonly consumed nonsteroidal anti-inflammatory drug (NSAID), in a placebo-controlled, counterbalanced crossover trial. Twelve men aged 20-26 consumed ibuprofen or placebo before and after HIIE at 120% maximum aerobic power. Multiple muscle biopsies were taken for tissue analysis before and after HIIE. p16INK4a+ cells were located surrounding myofibers in muscle tissues. The maximum decrease in p16INK4a mRNA levels within muscle tissues occurred at 3 h post-exercise (-82%, p < 0.01), gradually recovering over the next 3-24 h. A concurrent reduction pattern in CD11b mRNA (-87%, p < 0.01) was also found within the same time frame. Ibuprofen treatment attenuated the post-exercise reduction in both p16INK4a mRNA and CD11b mRNA. The strong correlation (r = 0.88, p < 0.01) between p16INK4a mRNA and CD11b mRNA in muscle tissues suggests a connection between the markers of tissue aging and pro-inflammatory myeloid differentiation. In conclusion, our results suggest that the senolytic effect of high-intensity exercise on human skeletal muscle is mediated by acute inflammation.
Assuntos
Anti-Inflamatórios não Esteroides , Estudos Cross-Over , Ibuprofeno , Inflamação , Músculo Esquelético , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Adulto , Ibuprofeno/farmacologia , Inflamação/metabolismo , Adulto Jovem , Anti-Inflamatórios não Esteroides/farmacologia , Exercício Físico/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/genética , Antígeno CD11b/metabolismo , Antígeno CD11b/genética , RNA Mensageiro/metabolismo , Treinamento Intervalado de Alta IntensidadeRESUMO
Endotoxin tolerance (ET) is the hyporesponsiveness to lipopolysaccharide (LPS) after prior exposure. It is characterized by the downregulation of pro-inflammatory cytokine levels. Although ET protects against inflammation, its abolishment or recovery is critical for immunity. Nitric oxide (NO) plays various roles in the development of ET; however, its specific role in ET recovery remains unknown. To induce ET, RAW264.7 cells (a murine macrophage cell line) were pre-exposed to LPS (LPS1, 100 ng/mL for 24 h) and subsequently re-stimulated with LPS (LPS2, 100 ng/mL for 24 h). Expression of cytokines, NO, nitrite and inducible NO synthase (iNOS) were measured after 0, 12, 24, and 36 h of resting after LPS1 treatment with or without the iNOS-specific inhibitor, 1400W. LPS2-induced tumor necrosis factor-⺠(TNF-âº) and interleukin-6 (IL-6) were downregulated after LPS1 treatment, confirming the development of ET. Notably, TNF-⺠and IL-6 levels spontaneously rebounded after 12-24 h of resting following LPS1 treatment. In contrast, levles of NO, nitrite and iNOS increased during ET development and decreased during ET recovery. Moreover, 1400W inhibited ET development and blocked the early production of NO (<12 h) during ET recovery. Our findings suggest a negative correlation between iNOS-induced NO and cytokine levels in the abolishment of ET.
Assuntos
Lipopolissacarídeos , Óxido Nítrico Sintase Tipo II , Óxido Nítrico , Fator de Necrose Tumoral alfa , Animais , Óxido Nítrico/metabolismo , Camundongos , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Interleucina-6/metabolismo , Endotoxinas/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
Cordyceps sinensis is a parasitic fungus known to induce immune responses. The impact of Cordyceps supplementation on stem cell homing and expansion to human skeletal muscle after exercise remains unexplored. In this study, we examined how pre-exercise Cordyceps supplementation influences cell infiltration, CD34+ cell recruitment, and Pax7+ cell expansion in human skeletal muscle after high-intensity interval exercise (HIIE) on a cycloergometer. A randomized, double-blind, placebo-controlled crossover study was conducted with 14 young adults (age: 24 ± 0.8 years). A placebo (1 g cornstarch) and Cordyceps (1 g Cordyceps sinensis) were administered before exercise (at 120% maximal aerobic power). Multiple biopsies were taken from the vastus lateralis for muscle tissue analysis before and after HIIE. This exercise regimen doubled the VEGF mRNA in the muscle at 3 h post-exercise (P = 0.006). A significant necrotic cell infiltration (+284%, P = 0.05) was observed 3 h after HIIE and resolved within 24 h. This response was substantially attenuated by Cordyceps supplementation. Moreover, we observed increases in CD34+ cells at 24 h post-exercise, notably accelerated by Cordyceps supplementation to 3 h (+51%, P = 0.002). This earlier response contributed to a four-fold expansion in Pax7+ cell count, as demonstrated by immunofluorescence double staining (CD34+/Pax7+) (P = 0.01). In conclusion, our results provide the first human evidence demonstrating the accelerated resolution of exercise-induced muscle damage by Cordyceps supplementation. This effect is associated with earlier stem cell recruitment into the damaged sites for muscle regeneration.
Assuntos
Cordyceps , Estudos Cross-Over , Exercício Físico , Músculo Esquelético , Humanos , Cordyceps/química , Adulto Jovem , Masculino , Exercício Físico/fisiologia , Adulto , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Método Duplo-Cego , Células-Tronco/efeitos dos fármacos , Antígenos CD34/metabolismo , Feminino , Fator de Transcrição PAX7/metabolismo , Fator de Transcrição PAX7/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
p16INK4a expression is a robust biomarker of senescence for stem cells in human tissues. Here we examined the effect of exercise intensity on in vivo senescence in skeletal muscle, using a randomized counter-balanced crossover design. Biopsied vastus lateralis of 9 sedentary men (age 26.1 ± 2.5 y) were assessed before and after a single bout of moderate steady state exercise (SSE, 60% maximal aerobic power) and high intensity interval exercise (HIIE, 120% maximal aerobic power) on a cycloergometer accumulating same amount of cycling work (in kilojoule). Increases in cell infiltration (+1.2 folds), DNA strand break (+1.3 folds), and γ-H2AX+ myofibers (+1.1 folds) occurred immediately after HIIE and returned to baseline in 24 h (p < 0.05). Muscle p16Ink4a mRNA decreased 24 h after HIIE (-57%, p < 0.05). SSE had no effect on cell infiltration, p16Ink4a mRNA, and DNA strand break in muscle tissues. Senescence-lowering effect of HIIE was particularly prominent in the muscle with high pre-exercise p16INK4a expression, suggesting that exercise intensity determines the level of selection pressure to tissue stem cells at late senescent stage in human skeletal muscle. This evidence provides an explanation for the discrepancy between destructive nature of high intensity exercise and its anti-aging benefits.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina , Senoterapia , Masculino , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Músculo Esquelético/metabolismo , Proteínas Inibidoras de Quinase Dependente de Ciclina/metabolismo , RNA Mensageiro/metabolismo , DNA/metabolismoRESUMO
There are many surgical operations performed daily in operation rooms worldwide. Adequate anesthesia is needed during an operation. Besides hypnosis, adequate analgesia is critical to prevent autonomic reactions. Clinical experience and vital signs are usually used to adjust the dosage of analgesics. Analgesia nociception index (ANI), which ranges from 0 to 100, is derived from heart rate variability (HRV) via electrocardiogram (ECG) signals, for pain evaluation in a non-invasive manner. It represents parasympathetic activity. In this study, we compared the performance of multilayer perceptron (MLP) and long short-term memory (LSTM) algorithms in predicting expert assessment of pain score (EAPS) based on patient's HRV during surgery. The objective of this study was to analyze how deep learning models differed from the medical doctors' predictions of EAPS. As the input and output features of the deep learning models, the opposites of ANI and EAPS were used. This study included 80 patients who underwent operations at National Taiwan University Hospital. Using MLP and LSTM, a holdout method was first applied to 60 training patients, 10 validation patients, and 10 testing patients. As compared to the LSTM model, which had a testing mean absolute error (MAE) of 2.633 ± 0.542, the MLP model had a testing MAE of 2.490 ± 0.522, with a more appropriate shape of its prediction curves. The model based on MLP was selected as the best. Using MLP, a seven-fold cross validation method was then applied. The first fold had the lowest testing MAE of 2.460 ± 0.634, while the overall MAE for the seven-fold cross validation method was 2.848 ± 0.308. In conclusion, HRV analysis using MLP algorithm had a good correlation with EAPS; therefore, it can play role as a continuous monitor to predict intraoperative pain levels, to assist physicians in adjusting analgesic agent dosage. Further studies may consider obtaining more input features, such as photoplethysmography (PPG) and other kinds of continuous variable, to improve the prediction performance.
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Analgesia , Aprendizado Profundo , Algoritmos , Analgesia/métodos , Humanos , Nociceptividade/fisiologia , DorRESUMO
Several plant compounds have been found to possess neuroactive properties. The aim of this study was to investigate the anticonvulsant effect of eupafolin, a major active component extracted from Salvia plebeia, a herb used in traditional medicine for its anti-inflammatory properties. To this end, we assessed the anticonvulsant effects of eupafolin in rats intraperitoneally (i.p.) injected with kainic acid (KA) to elucidate this mechanism. Treatment with eupafolin (i.p.) for 30 min before KA administration significantly reduced behavioral and electrographic seizures induced by KA, similar to carbamazepine (i.p.), a widely used antiepileptic drug. Eupafolin treatment also significantly decreased KA seizure-induced neuronal cell death and glutamate elevation in the hippocampus. In addition, eupafolin notably reversed KA seizure-induced alterations in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR2, glutamate decarboxylase 67 (GAD67, GABAergic enzyme), and Wnt signaling-related proteins, including porcupine, Wnt1, phosphorylated-glycogen synthase kinase-3ß, ß-catenin, and Bcl-2 in the hippocampus. Furthermore, the increased level of Dickkopf-related protein 1 (Dkk-1, a Wnt signaling antagonist) and the decreased level of Disheveled1 (Dvl-1, a Wnt signaling activator) in the hippocampus of KA-treated rats were reversed by eupafolin. This study provides evidence of the anticonvulsant and neuroprotective properties of eupafolin and of the involvement of regulation of glutamate overexcitation and Wnt signaling in the mechanisms of these properties. These findings support the benefits of eupafolin in treating epilepsy.
Assuntos
Flavonas , Fármacos Neuroprotetores , Via de Sinalização Wnt , beta Catenina , Animais , Anticonvulsivantes/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Flavonas/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/toxicidade , Fármacos Neuroprotetores/uso terapêutico , Ratos , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo , Regulação para Cima , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismoRESUMO
BACKGROUND/PURPOSE: Residents play an important role as teachers of junior colleagues and medical students. Clinical teaching also helps residents in clinical learning. However, the skills required for residents to be competent teachers are rarely described systemically. Beyond the widely adopted six core competencies for postgraduate training by the Accreditation Council for Graduate Medical Education (ACGME), the teaching competencies should be further developed, and the milestones should be clearly defined to serve as better references for resident training programs. METHODS: Twenty members, including five experts from major teaching hospitals across Taiwan and 15 from a public medical center, were invited to a workgroup to collaboratively develop a competency-based framework. The development process was similar to that suggested by the ACGME. The teaching competencies framework were drafted by an experienced physician educator. The draft was sent to each group member, and feedback was collected. Two workgroup meetings were held for consensus formation. The contents of the teaching competencies of residents were confirmed after two rounds of revision. The outline of the framework was also reported at an international meeting in September 2019. RESULTS: Two core competencies, instruction and assessment, with three sub-competencies and 37 milestones, were adopted in the final edition of resident-as-teacher competencies. The sub-competencies were "dissemination of knowledge" and "teaching of procedural skills" for instruction, and "direct observation and feedback" for assessment. CONCLUSION: A competency-based framework for resident-as-teacher was developed. The framework can be applied in combination with other existing competencies for holistic postgraduate training programs.
Assuntos
Internato e Residência , Acreditação , Competência Clínica , Educação de Pós-Graduação em Medicina , Docentes de Medicina , HumanosRESUMO
BACKGROUND: Stem cell aging, characterized by elevated p16INK4a expression, decreases cell repopulating and self-renewal abilities, which results in elevated inflammation and slow recovery against stress. METHODS: Biopsied muscles were analyzed at baseline and 24 h after squat exercise in 12 trained men (22 ± 2 y). Placebo (PLA) and immunostimulant Rg1 (5 mg) were supplemented 1 h before a squat exercise, using a double-blind counterbalanced crossover design. RESULTS: Perceived exertion at the end of resistance exercise session was significantly lowered after Rg1 supplementation. Exercise doubled endothelial progenitor cells (EPC) (p < 0.001) and decreased p16INK4a mRNA to 50% of baseline (d = 0.865, p < 0.05) in muscle tissues, despite p16INK4a+ cell and beta-galactosidase+ (ß-Gal+) cell counts being unaltered. Rg1 further lowered p16INK4a mRNA to 35% of baseline with greater effect size than the PLA level (d = 1.302, p < 0.01) and decreased myeloperoxidase (MPO) mRNA to 39% of baseline (p < 0.05). A strong correlation between MPO and p16INK4a expression in muscle tissues was observed (r = 0.84, p < 0.001). CONCLUSION: EPC in skeletal muscle doubled 1 d after an acute bout of resistance exercise. The exercised effects in lowering EPC aging and tissue inflammation were enhanced by immunostimulant Rg1, suggesting the involvement of immune stimulation on EPC rejuvenation.
Assuntos
Senescência Celular , Exercício Físico/fisiologia , Ginsenosídeos/farmacologia , Músculo Esquelético/fisiologia , Células-Tronco/citologia , Biomarcadores/metabolismo , Senescência Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Humanos , Masculino , Músculo Esquelético/efeitos dos fármacos , Peroxidase/genética , Peroxidase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células-Tronco/efeitos dos fármacos , Adulto JovemRESUMO
INTRODUCTION: THP-1 cells, a human leukemia monocytic cell line, differentiated by phorbol myristate acetate (PMA) are widely used as surrogate of human macrophages. Differentiated THP-1 cells acquire macrophage-like characteristics including more adherence and altered cell function. Nitric oxide (NO), an intracellular messenger, is critical in regulating cell differentiation. Here we elucidated whether NO relates to PMA-induced monocyte-to-macrophage differentiation of THP-1 cells. The mutual regulation of calcium and NO was also investigated. MATERIAL & METHODS: THP-1 cells were incubated with PMA for 24 h, followed by assay of adherence, morphological change, migration or IL-1ß release. L-NG-Nitroarginine methyl ester (l-NAME, a nitric oxide synthase inhibitor) or BAPTA-AM (a calcium chelator) was added before PMA stimulation, and levels of calcium and NO were measured. Furthermore, a selective inhibitor of inducible nitric oxide synthase (iNOS) activity was employed to study the role of iNOS. RESULTS AND DISCUSSION: Effects of PMA on upregulation of adherence, lipopolysaccharide-triggered IL-1ß, and migration ability of THP-1 cells were consistent with NO concentrations. Both l-NAME and BAPTA-AM mitigated effects of PMA on THP-1 cells differentiation. BAPTA-AM decreased levels of NO, while l-NAME had no effect on calcium levels. Of note, inhibition of iNOS activity decreased PMA-triggered upregulation of NO. CONCLUSION: PMA induced differentiation of THP-1 cells partially in a NO-dependent manner. The calcium signaling may mediate PMA-triggered upregulation of NO.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Humanos , Macrófagos/metabolismo , Monócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Células THP-1 , Regulação para Cima/efeitos dos fármacosRESUMO
Aerobic exercise induces oxidative stress and DNA damage, nevertheless, lowers cancer incidence. It remains unclear how genetic stability is maintained under this condition. Here, we examined the dynamic change of the tumor suppressor p16INK4a in cells of skeletal muscle among young men following 60-min of aerobic cycling at 70% maximal oxygen consumption (VÌO2max). Rg1 (5 mg, an immunostimulant ginsenoside) and placebo (PLA) were supplemented 1 h before exercise. Data from serial muscle biopsies shows unchanged p16INK4a+ cells after exercise followed by a considerable increase (+21-fold) in vastus lateralis muscle 3 h later. This increase was due to the accumulation of endothelial progenitor cells (p16INK4a+/CD34+) surrounding myofibers and other infiltrated nucleated cells (p16INK4a+/CD34-) in necrotic myofibers. During the Rg1 trial, acute increases of p16INK4a+ cells in the muscle occurred immediately after exercise (+3-fold) and reversed near baseline 3 h later. Rg1 also lowered IL-10 mRNA relative to PLA 3 h after exercise. Post-exercise increases in VEGF mRNA and CD163+ macrophages were similar for PLA and Rg1 trials. Conclusion: The marked increases in p16INK4a protein expression of endothelial progenitor cells in skeletal muscle implicates a protective mechanism for maintaining genetic stability against aerobic exercise. Rg1 accelerates resolution of the exercise-induced stress response.
Assuntos
Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Células Progenitoras Endoteliais/metabolismo , Exercício Físico , Contração Muscular , Músculo Quadríceps/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Ciclismo , Estudos Cross-Over , Inibidor p16 de Quinase Dependente de Ciclina/genética , Dano ao DNA , Regulação para Baixo , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/patologia , Ginsenosídeos/administração & dosagem , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Necrose , Estresse Oxidativo , Consumo de Oxigênio , Músculo Quadríceps/efeitos dos fármacos , Músculo Quadríceps/patologia , Receptores de Superfície Celular/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
Naturally occurring tumor in animals receiving high minerals from deep oceans (DOM: hardness 600 mg/L) from 6 months of age until natural death was firstly assessed in 200 Sprague Dawley rats, randomized into four groups: Control (C), DOM (D), Fructose (F), and Fructose + DOM (FD). Fructose drink contained 11% fructose. Tumor incidence (necropsy at death) in the D group was ~40% lower than that in the C group (P < .05), together with lower body mass gain and greater locomotive activity during their initial 18 months (P < .05) but not during later life. X-ray image analysis on abnormal solid tissue among survivors at 18 and 24 months of age confirms a similar trend, exhibiting ~50% and ~65% lower tumor incidence than the C and F groups, respectively. Reduced-to-oxidized glutathione ratio (GSH/GSSG) declined with age for the first three quarters of life on all groups (P < .05), followed by a resurgence during end-life among survivors at 24 months. This resurgence is markedly associated with lower tumor expansion but unrelated with DOM supplementation. Our results demonstrate valuable application of minerals and trace elements from deep oceans, as a vastly available natural source, on tumor suppression during normal aging.
Assuntos
Carcinogênese/efeitos dos fármacos , Frutose/toxicidade , Minerais/farmacologia , Neoplasias Experimentais/prevenção & controle , Edulcorantes/toxicidade , Animais , Carcinogênese/patologia , Feminino , Expectativa de Vida , Masculino , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/patologia , Oceanos e Mares , Ratos , Ratos Sprague-DawleyRESUMO
The Nod-like receptor protein 3 (NLRP3) inflammasome is a multi-protein complex composed of NLRP3, pro-caspase-1, and apoptosis-associated speck-like protein that contains a caspase recruitment domain (ASC). After NLRP3 priming by lipopolysaccharide (LPS), the ligand of toll-like receptor 4 (TLR4), activation of the NLRP3 inflammasome triggers caspase-1 maturation, leading to pyroptosis and release of interleukin-1beta (IL-1beta). Expression of TLR4 modulates LPS-triggered inflammatory cascades as well as the NLRP3 signaling. L-type calcium channel antagonists are widely used as anti-hypertensive drugs and also exert anti-inflammatory effects through inhibiting release of cytokines including IL-1beta. However, few studies reveal effects of L-type calcium channel antagonists on the NLRP3 inflammasome. In this study, we investigated the effects of nicardipine and verapamil, both L-type calcium channel antagonists, on the NLRP3 inflammasome using differentiated THP-1 cells. Pyroptosis or levels of IL-1beta and caspase-1 were assayed by flow cytometry or enzyme-linked immunosorbent assay, respectively. ASC oligomerization was assayed by immunofluorescence microscopy. Expression of NLRP3 or TLR4 was assayed by polymerase chain reaction and immunoblotting. Nuclear factor-kappaB (NF-kappaB) pathway was also studied. Our results showed that pyroptosis and IL-1beta release were attenuated by nicardipine, but not verapamil. Nicardipine also mitigated caspase-1 activation, inhibited ASC oligomerization, and reduced NLRP3 expression. Furthermore, nicardipine downregulated phosphorylation or nuclear translocation of NF-kappaB p65, consistent with the inhibitory effect of nicardipine on LPS-induced TLR4 expression. In conclusion, nicardipine exerted anti-inflammatory effects through inhibiting NLRP3 inflammasome pathway. Nicardipine may mitigate NLRP3 priming via inhibiting NF-kappaB activation, mediated by suppressing LPS-induced TLR4 expression.
Assuntos
Lipopolissacarídeos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/biossíntese , Nicardipino/farmacologia , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/biossíntese , Bloqueadores dos Canais de Cálcio/farmacologia , Expressão Gênica , Humanos , Células THP-1/efeitos dos fármacos , Células THP-1/metabolismoRESUMO
It remains unclear how exercise, as an entropic event, brings benefit against human aging. Here we examined longitudinal changes of p16Ink4a+ senescent cells in skeletal muscle of young men (aged 22.5±1.7 y) before and after resistance exercise (0 h and 48 h) with multiple biopsies at two different protein availabilities: low protein (14%) and isocaloric high protein (44%) supplemented conditions. Immunohistochemistry analysis of muscle cross-sections using p16Ink4a and CD34 antibodies confirmed that the detected senescent cells were endothelial progenitor cells. Leukocyte infiltration into skeletal muscle increased during resistance exercise. The senescent cells in muscle decreased (-48%, P < 0.01) after exercise for 48 h. Low protein supplementation resulted in greater infiltrations of both CD68+ phagocytic macrophage and leukocyte, further decreased p16Ink4a+ senescent cells (-73%, P < 0.001), and delayed increases in regenerative CD163+ macrophage in skeletal muscle, compared with high protein supplemented condition. Significant gain in muscle mass after 12 weeks of training occurred only under high protein supplemented condition. CONCLUSION: Rapid senescent cell clearance of human skeletal muscle during resistance exercise seems to associate with enhanced in situ phagocytosis. High protein availability accelerates resolution of muscle inflammation and promotes muscle increment after training.
Assuntos
Senescência Celular/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/fisiologia , Treinamento Resistido , Humanos , Leucócitos/fisiologia , Masculino , Adulto JovemRESUMO
Lycopene is a natural dietary carotenoid that was reported to exhibit a neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca2+ concentration elevation. The inhibitory effect of lycopene on 4-AP-evoked glutamate release was markedly reduced in the presence of the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was insensitive to the intracellular Ca2+-release inhibitors dantrolene and CGP37157. Furthermore, in the presence of the protein kinase C inhibitors GF109203X and Go6976, the action of lycopene on evoked glutamate release was prevented. These results are the first to suggest that lycopene inhibits glutamate release from rat cortical synaptosomes by suppressing presynaptic Ca2+ entry and protein kinase C activity.
Assuntos
Cálcio/metabolismo , Carotenoides/farmacologia , Ácido Glutâmico/metabolismo , Proteína Quinase C/antagonistas & inibidores , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Carbazóis/farmacologia , Interações Medicamentosas , Indóis/farmacologia , Licopeno , Masculino , Maleimidas/farmacologia , Neurotransmissores/metabolismo , Ratos , Ratos Sprague-Dawley , Sinapses/efeitos dos fármacosRESUMO
BACKGROUND: Existing literature on anti-oxidant capacity of ginseng has been inconsistent due to variance in the profile of ginseng steroids (Ginsenosides) that is because of differences in seasons and species. METHODS: We used various doses of ginseng steroids to determine its effect on oxidative stress and anti-oxidant capacity of rat skeletal muscle against exercise. RESULTS: Under non-exercise conditions, we found increased thiobarbituric acid reactive substance (TBARS) levels and decreased reduced/oxidized glutathione ratio (GSH/GSSG) in rat skeletal muscle as dose increases (p < 0.05), which indicates the pro-oxidant property of ginseng steroids at baseline. Intriguingly, exhaustive exercise-induced increased TBARS and decreased GSH/GSSG ratio were attenuated with low and medium doses of ginseng steroids (20 and 40 mg per kg), but not with high dose (120 mg per kg). At rest, anti-oxidant enzyme activities, including catalase (CAT), glutathione reductase (GR) and glutathione S-transferase (GST) were increased above vehicle-treated level, but not with the high dose, suggesting a hormetic dose-response of ginseng steroids. CONCLUSION: The results of this study provide an explanation for the inconsistent findings on anti-oxidative property among previous ginseng studies. For optimizing the anti-oxidant outcome, ginseng supplementation at high dose should be avoided.
RESUMO
BACKGROUND: Deep oceans have been suggested as a possible site where the origin of life occurred. Along with this theoretical lineage, experiments using components from deep ocean water to recreate life is underway. Here, we propose that if terrestrial organisms indeed evolved from deep oceans, supply of deep ocean mineral water (DOM) to humans, as a land creature, may replenish loss of molecular complexity associated with evolutionary sea-to-land migration. METHODS: We conducted a randomized, double-blind, placebo-controlled crossover human study to evaluate the effect of DOM, taken from a depth of 662 meters off the coast of Hualien, Taiwan, on time of recovery from a fatiguing exercise conducted at 30°C. RESULTS: The fatiguing exercise protocol caused a protracted reduction in aerobic power (reduced VO2max) for 48 h. However, DOM supplementation resulted in complete recovery of aerobic power within 4 h (P < 0.05). Muscle power was also elevated above placebo levels within 24 h of recovery (P < 0.05). Increased circulating creatine kinase (CK) and myoglobin, indicatives of exercise-induced muscle damage, were completely eliminated by DOM (P < 0.05) in parallel with attenuated oxidative damage (P < 0.05). CONCLUSION: Our results provide compelling evidence that DOM contains soluble elements, which can increase human recovery following an exhaustive physical challenge.
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BACKGROUND AND OBJECTIVE: the objective of this study was to assess whether antiemetic drugs metoclopramide and diphenhydramine, administered together as opposed to alone, can have better efficacy in preventing postoperative nausea and vomiting when added to patient-controlled morphine analgesia. PATIENTS AND METHODS: during the period July 2007 to August 2008, 200 women scheduled for abdominal total hysterectomy were randomised to one of four postoperative, patient-controlled analgesia regimens: group 1, morphine 1 mg ml; group 2, morphine 1 mg ml with metoclopramide 0.5 mg ml; group 3, morphine 1 mg ml with diphenhydramine 0.6 mg ml; and group 4, morphine 1 mg ml with metoclopramide 0.5 mg ml and diphenhydramine 0.6 mg ml. Dexamethasone 4 mg was administered to all patients in all groups after anaesthesia induction as a prophylactic antiemetic medication, and prochlorperazine 5 mg was administered by intramuscular injection as necessary as a salvage/rescue therapy. Nausea, vomiting, pruritus, level of sedation, pain and morphine consumption were compared between the four groups. RESULTS: the incidence of nausea was significantly (P < 0.05) lower in group 4 compared to the other groups. In addition, there was a significant (P = 0.006) difference in the incidence of vomiting between groups 1 and 4. Repeated measurement analysis showed that numeric rating scale scores for group 4 were significantly (P < 0.001) lower than those for the other groups. CONCLUSION: results of this study showed that a combination of metoclopramide with diphenhydramine in patients treated with dexamethasone at anaesthesia induction decreased postoperative nausea and vomiting compared to metoclopramide or diphenhydramine in these patients, when added to patient-controlled anaesthesia with morphine.
Assuntos
Antieméticos/uso terapêutico , Difenidramina/uso terapêutico , Metoclopramida/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Antieméticos/administração & dosagem , Dexametasona/uso terapêutico , Difenidramina/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Histerectomia/métodos , Metoclopramida/administração & dosagem , Pessoa de Meia-Idade , Morfina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Proclorperazina/uso terapêuticoRESUMO
We present a case of splenic rupture as the cause of a sudden drop in blood pressure soon after mitral valve surgery for infective endocarditis. This case suggests that, in addition to more common causes of unstable vital signs after valvular surgery, such as cardiac tamponade or bleeding at the operation site, splenic rupture, although rare, should be considered in the differential diagnosis. This is particularly important in the case of infective endocarditis.
Assuntos
Endocardite/cirurgia , Valva Mitral/cirurgia , Complicações Pós-Operatórias/etiologia , Ruptura Esplênica/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Radiografia , Ruptura Esplênica/diagnóstico por imagem , Ruptura Esplênica/cirurgiaRESUMO
We report a 20-year-old male patient with preoperatively undiagnosed myocarditis, who received general anesthesia for laparoscopic appendectomy. Because of arrhythmia, a cardiologist was consulted postoperatively. The 12-lead electrocardiogram showed complete atrioventricular block and the echocardiogram showed global hypokinesia of the left ventricle with impaired contractility, a left ejection fraction of 37%, and a dilated right heart. Subsequently, a permanent pacemaker was implanted and the patient was discharged from hospital without any complications.