RESUMO
The brain is assumed to be hypoactive during cardiac arrest. However, animal models of cardiac and respiratory arrest demonstrate a surge of gamma oscillations and functional connectivity. To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations, and increased interhemispheric functional and directed connectivity in gamma bands. High-frequency oscillations paralleled the activation of beta/gamma cross-frequency coupling within the somatosensory cortices. Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical "hot zone," a region postulated to be critical for conscious processing. This gamma activity was stimulated by global hypoxia and surged further as cardiac conditions deteriorated in the dying patients. These data demonstrate that the surge of gamma power and connectivity observed in animal models of cardiac arrest can be observed in select patients during the process of dying.
Assuntos
Encéfalo , Parada Cardíaca , Animais , Humanos , Raios gama , Encéfalo/fisiologia , Eletroencefalografia , CoraçãoRESUMO
Sudden death is an important but underrecognized consequence of stroke. Acute stroke can disturb central control of autonomic function and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in the spontaneously hypertensive stroke-prone rat strain (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from nine SHRSP and eight Wistar-Kyoto (WKY) rats. RR interval was analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 h, whereas no mortality was observed in WKY rats. The functionality of both the brain and the heart were significantly altered in SHRSP compared with WKY rats after BCCAL. SHRSP, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of forebrain ischemia-induced sudden death. NEW & NOTEWORTHY This study demonstrates a marked surge of corticocardiac coupling in rats dying from focal cerebral ischemia, consistent with our earlier data in rats exposed to fatal asphyxia. Since the bidirectional electrical signal coupling (corticocardiac coherence) and communication (corticocardiac connectivity) between the brain and the heart are only identified in dying animals, they could be used as potential biomarkers to predict the risk of sudden death.
Assuntos
Isquemia Encefálica/fisiopatologia , Ondas Encefálicas , Morte Súbita Cardíaca , Frequência Cardíaca , Prosencéfalo/fisiopatologia , Animais , Pressão Sanguínea , Coração/fisiopatologia , Prosencéfalo/irrigação sanguínea , Ratos , Ratos WistarRESUMO
The mechanism by which the healthy heart and brain die rapidly in the absence of oxygen is not well understood. We performed continuous electrocardiography and electroencephalography in rats undergoing experimental asphyxia and analyzed cortical release of core neurotransmitters, changes in brain and heart electrical activity, and brain-heart connectivity. Asphyxia stimulates a robust and sustained increase of functional and effective cortical connectivity, an immediate increase in cortical release of a large set of neurotransmitters, and a delayed activation of corticocardiac functional and effective connectivity that persists until the onset of ventricular fibrillation. Blocking the brain's autonomic outflow significantly delayed terminal ventricular fibrillation and lengthened the duration of detectable cortical activities despite the continued absence of oxygen. These results demonstrate that asphyxia activates a brainstorm, which accelerates premature death of the heart and the brain.
Assuntos
Asfixia/complicações , Asfixia/fisiopatologia , Córtex Cerebral/fisiopatologia , Parada Cardíaca/complicações , Parada Cardíaca/fisiopatologia , Coração/fisiopatologia , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Eletrocardiografia , Eletroencefalografia , Potenciais Evocados , Testes de Função Cardíaca , Frequência Cardíaca , Masculino , Neurotransmissores/metabolismo , Ratos Wistar , Fatores de Tempo , Fibrilação Ventricular/complicações , Fibrilação Ventricular/fisiopatologiaRESUMO
Cytochrome b5 reductase 2 (CYB5R2), a member of the flavoprotein pyridine nucleotide cytochrome reductase family, is associated with a number of physiological reactions. However, its role in cancer, especially nasopharyngeal carcinoma (NPC), has not been addressed. Here, we investigate the transcript levels and promoter methylation status of CYB5R2 in NPC derived cell lines and tumor biopsies and experimentally address its role as a tumor suppressor gene. We find that CYB5R2 transcript levels are decreased in NPC cell lines and tumor biopsies. Promoter hypermethylation of CYB5R2 was detected in all six tested NPC cell lines and in 84% of primary NPC tumor biopsies but not in normal nasopharyngeal epithelium. Clinically, CYB5R2 methylation was associated with lymph node metastasis in NPC patients (P < 0.05). The endogenous expression of CYB5R2 could be restored in vitro by the methyltransferase inhibitor 5-aza-2'-deoxycytidine in NPC cell lines. Ectopic expression of CYB5R2 had an inhibitory effect on proliferation, clonogenicity and migration of NPC cells. Moreover, in vivo tests in nude mice indicated that ectopic expression of CYB5R2 reduces the tumorigenicity of CYB5R2-negative NPC cells. Collectively, these findings suggest that CYB5R2 may be a functional tumor suppressor gene, frequently inactivated by hypermethylation of its promoter in NPC. We report here the first instance of epigenetic downregulation in NPC tumor biopsies of a key enzyme, CYB5R2, which is responsible for the detoxification of environmental carcinogens. We propose the possibility of utilizing CYB5R2 promoter methylation as a diagnostic biomarker of NPC in the future.
Assuntos
Citocromo-B(5) Redutase/genética , Metilação de DNA , Genes Supressores de Tumor , Neoplasias Nasofaríngeas/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Animais , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Biomarcadores Tumorais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Decitabina , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-IdadeRESUMO
Objective:To investigate the long-term effect of partial tonsillectomy in children with tonsil hypertrophy. Methods:A total of 146 children with obstructive sleep apneaï¼OSAï¼ who received surgical treatment for tonsil hyperplasia from January 2010 to January 2013 were selected and divided into the observation groupï¼n=69ï¼ and the control groupï¼n=77ï¼. The observation group was received tonsillotomyï¼TTï¼, and the control group was received total tonsillectomyï¼TEï¼. Parental satisfaction and OSA quality of life questionnaire for childrenï¼OSA-18ï¼ were surveyed. Residual tonsil size was measured, and polysomnographyï¼PSGï¼ was monitored after 10 years. HE and immunohistochemical analysis were performed on tonsil tissues of one patient who performed a second operation after TT in 2017 year. Results:The results of questionnaire survey showed that the symptoms of respiratory obstruction were significantly improved in both groups, and the satisfaction of TT group was higher than that in the TE group. No increase in the number of respiratory tract infections was observed in all patients. In the TT group, nine casesï¼13.04%ï¼ had tonsil hyperplasia toâ ¡°, and the remaining patients had tonsil hyperplasia to â °. In addition, one case hadtonsil suppurative infection at the 14th month after surgery, and no recurrence or reoperation was found after treatment. There were seven cases in the TT group and eight cases in the TE group with occasional snoring and mouth breathing after surgery, but the PSG examination of the patients did not meet the diagnosis of OSA. The main causes were obesity and allergic rhinitis. Compared with the first operation, the cicatricial obstruction and infection of tonsil tissue in the second operation were not significantly changed, and the immunohistochemical results also demonstrated that the expression of CD20 was not changed, and the expression of CD3 was decreased. Conclusion:Both TT and TE can effectively improve the symptoms of OSA obstruction in children. TT has less trauma, less postoperative pain, faster recovery and lower rate of hyperplasia, which can be used as one of the main methods for the treatment of tonsil hypertrophy in children.
Assuntos
Hiperplasia , Hipertrofia , Tonsila Palatina , Apneia Obstrutiva do Sono , Tonsilectomia , Humanos , Tonsilectomia/métodos , Apneia Obstrutiva do Sono/cirurgia , Criança , Masculino , Feminino , Hiperplasia/cirurgia , Tonsila Palatina/cirurgia , Tonsila Palatina/patologia , Hipertrofia/cirurgia , Resultado do Tratamento , Qualidade de Vida , Inquéritos e Questionários , Polissonografia , Pré-Escolar , Satisfação do Paciente , ReoperaçãoRESUMO
What happens in the human brain when we are unconscious? Despite substantial work, we are still unsure which brain regions are involved and how they are impacted when consciousness is disrupted. Using intracranial recordings and direct electrical stimulation, we mapped global, network, and regional involvement during wake vs. arousable unconsciousness (sleep) vs. non-arousable unconsciousness (propofol-induced general anesthesia). Information integration and complex processing we`re reduced, while variability increased in any type of unconscious state. These changes were more pronounced during anesthesia than sleep and involved different cortical engagement. During sleep, changes were mostly uniformly distributed across the brain, whereas during anesthesia, the prefrontal cortex was the most disrupted, suggesting that the lack of arousability during anesthesia results not from just altered overall physiology but from a disconnection between the prefrontal and other brain areas. These findings provide direct evidence for different neural dynamics during loss of consciousness compared with loss of arousability.
Assuntos
Estado de Consciência , Propofol , Humanos , Estado de Consciência/fisiologia , Inconsciência/induzido quimicamente , Propofol/farmacologia , Encéfalo/fisiologia , Anestesia Geral , EletroencefalografiaRESUMO
Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine's antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects. We analyzed oscillatory changes after subsequent propofol administration, whose GABAergic activity antagonizes ketamine's NMDA-mediated disinhibition, alongside a shared HCN1 inhibitory effect, to identify dynamics attributable to NMDA-mediated disinhibition versus HCN1 inhibition. Our results suggest that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of brain dynamic biomarkers and novel therapeutics for depression.
Assuntos
Ketamina , Propofol , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico , Propofol/farmacologia , N-Metilaspartato , Neurofisiologia , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Córtex Cerebral/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Cotton fibers, as natural fibers, are widely used in the textile industry in the world. In order to find genes involved in fiber development, a cDNA (designated as GhMADS11) encoding a novel MADS protein with 151 amino acid residues was isolated from cotton fiber cDNA library. The deduced protein shares high similarity with Arabidopsis AP1 and AGL8 in MADS domain. However, the GhMADS11 protein (being absent of the partial K-domain and normal C-terminus) is shorter than AP1 and AGL8 by the reason of gene frameshift mutation during evolution. The experimental results revealed that GhMADS11 was not a transcriptional activator, and it did not form homodimer. GhMADS11 transcripts were specifically accumulated in elongating fibers, but no or very low signals of its expression were detected in other tissues of cotton. Overexpression of GhMADS11 in fission yeast promotes atypical cell elongation by 1.4-2.0-fold. Furthermore, morphological analysis indicated that the transformed cells expressing GhMADS11m, a MIKC-type derivative of GhMADS11 by the site-directed mutation, displayed the same phenotype as that of the transformed cells with GhMADS11. The concurrence of these data sets suggested that GhMADS11 protein may function in fiber cell elongation, and its MADS domain and partial K-domain are sufficient for this function.
Assuntos
Genes de Plantas , Gossypium/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , DNA Complementar , Dimerização , Mutação da Fase de Leitura , Gossypium/citologia , Dados de Sequência Molecular , Filogenia , Proteínas de Plantas/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Técnicas do Sistema de Duplo-HíbridoRESUMO
Description of strategies for preventing surgical complications in the treatment of laryngeal carcinomas associated with giant thyroid cancer. For this study, the clinical data of an elderly patient with laryngeal carcinoma associated with a large thyroid tumor, diabetes and hypertension were used. The patient's tumor was removed with simultaneous surgery performed by the thyroid surgery department and the laryngeal surgery department; the patient was followed for more than 3 years and the scars of tracheal granulation and laryngeal adhesions were removed with repeated laser interventions. The literature review was carried out on the Wanfang database, on the China How Net database and on the MEDLINE database via Computer. The final research keywords used for the study were "squamous cell carcinoma" and "glottis" or "larynx" / "larynx", "surgery", "thyroid cancer" and "simultaneous surgery". RESULTS: After completion of the intervention, the nasogastric tube and tracheal cannula were successfully removed, the glottis was successfully reconstituted and oral respiration, phonation and oral feeding were normally resumed. CONCLUSION: The multidisciplinary approach for the simultaneous removal of a laryngeal carcinoma associated with a bulky thyroid tumor in elderly subjects with multi-system and multi-organ damage has been successfully implemented. There are only a few such cases presented in the literature to illustrate risk prevention strategies for postoperative complications, including postoperative infection, extubation difficulties and loss of speech, which deserve to be known. KEY WORDS: Glottic carcinoma, Thyroid tumor, Laser surgery multidisciplinary, Tracheal cannula, Vocal cords.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias da Glândula Tireoide , Idoso , Carcinoma de Células Escamosas/cirurgia , Glote/patologia , Glote/cirurgia , Humanos , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Prega Vocal/patologia , Prega Vocal/cirurgiaRESUMO
Melatonin deficiency has been proposed to underlie higher risks for cardiovascular and several other diseases in humans experiencing prolonged shiftwork. However, melatonin secretion has not been monitored longitudinally during consecutive shifts of the light:dark (LD) cycles in the same individuals (animals or humans) and the extent of melatonin deficiency is unknown in individuals experiencing consecutive LD shifts. We investigated the effect of consecutive LD shifts on melatonin secretion in adult F344 rats using continuous online pineal-microdialysis. The rats were entrained to the 12â¯h:12â¯h LD cycle before the shifts. The LD cycle was then advanced (n=5) or delayed (n=4) for six hours every four days for four consecutive times. The rats exhibited marked asymmetry in response to delay or advance LD shifts. While rats exposed to the repeated LD delay shifts always exhibited melatonin secretion throughout the entire periods, repeated LD advance shifts suppressed nocturnal melatonin secretion for several consecutive days in the middle of the 3-week period. Moreover, melatonin offset after LD delay and melatonin onset after LD advance determined the rate of circadian pacemaker reentrainment. Additionally, melatonin offset was phase locked at the new dark/light junctions for days following LD advance. These data demonstrate that chronic LD shifts are deleterious to melatonin rhythms, and that this effect is much more pronounced during advance shifts. These data may enhance our understanding of impact of LD shifts on our circadian timing system and benefit better design of shiftwork schedules to avoid melatonin disruption.
RESUMO
Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2-mediated asphyxic cardiac arrest model. Rats received either saline, phentolamine, atenolol, or phentolamine plus atenolol, 30 min before the onset of asphyxia. Electrocardiogram (ECG) and electroencephalogram (EEG) signals were simultaneously collected from each rat during the entire process and investigated for cardiac and brain functions using a battery of analytic tools. We found that adrenergic blockade significantly suppressed the initial decline of cardiac output, prolonged electrical activities of both brain and heart, asymmetrically altered functional connectivity within the brain, and altered, bi-directionally and asymmetrically, functional, and effective connectivity between the brain and heart. The protective effects of adrenergic blockers paralleled the suppression of brain and heart connectivity, especially in the right hemisphere associated with central regulation of sympathetic function. Collectively, our results demonstrate that blockade of brain-heart connection via alpha- and beta-adrenergic blockers significantly prolonged the detectable activities of both the heart and the brain in asphyxic rat. The beneficial effects of combined alpha and beta blockers may help extend the survival of cardiac arrest patients.
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PURPOSE: Promoter hypermethylation of tumor suppressor genes may serve as a promising biomarker for the diagnosis of cancer. Cell-free circulating DNA (cf-DNA) shares hypermethylation status with primary tumors. This study investigated promoter hypermethylation of five tumor suppressor genes as markers in the detection of nasopharyngeal carcinoma (NPC) in serum samples. METHODS: cf-DNA was extracted from serum collected from 40 NPC patients and 41 age- and sex-matched healthy subjects. The promoter hypermethylation status of the five genes (RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1) was assessed by methylation-specific PCR after sodium bisulfite conversion. Differences in the methylation status of these five genes between NPC patients and healthy subjects were compared. RESULTS: The concentration of cf-DNA in the serum of NPC patients was significantly higher than that in normal controls. The five tumor suppressor genes - RASSF1, CDKN2A, DLEC1, DAPK1 and UCHL1 - were found to be methylated in 17.5%, 22.5%, 25.0%, 51.4% and 64.9% of patients, respectively. The combination of four-gene marker - CDKN2A, DLEC1, DAPK1 and UCHL1 - had the highest sensitivity and specificity in predicting NPC. CONCLUSION: Screening DNA hypermethylation of tumor suppressor genes in serum was a promising approach for the diagnosis of NPC.