RESUMO
BACKGROUND: Previous research suggests that sevoflurane anesthesia may prevent the brain from accessing rapid eye movement (REM) sleep. If true, then patterns of neural activity observed in REM-on and REM-off neuronal populations during recovery from sevoflurane should resemble those seen after REM sleep deprivation. In this study, the authors hypothesized that, relative to controls, animals exposed to sevoflurane present with a distinct expression pattern of c-Fos, a marker of neuronal activation, in a cluster of nuclei classically associated with REM sleep, and that such expression in sevoflurane-exposed and REM sleep-deprived animals is largely similar. METHODS: Adult rats and Targeted Recombination in Active Populations mice were implanted with electroencephalographic electrodes for sleep-wake recording and randomized to sevoflurane, REM deprivation, or control conditions. Conventional c-Fos immunohistochemistry and genetically tagged c-Fos labeling were used to quantify activated neurons in a group of REM-associated nuclei in the midbrain and basal forebrain. RESULTS: REM sleep duration increased during recovery from sevoflurane anesthesia relative to controls (157.0 ± 24.8 min vs. 124.2 ± 27.8 min; P = 0.003) and temporally correlated with increased c-Fos expression in the sublaterodorsal nucleus, a region active during REM sleep (176.0 ± 36.6 cells vs. 58.8 ± 8.7; P = 0.014), and decreased c-Fos expression in the ventrolateral periaqueductal gray, a region that is inactive during REM sleep (34.8 ± 5.3 cells vs. 136.2 ± 19.6; P = 0.001). Fos changes similar to those seen in sevoflurane-exposed mice were observed in REM-deprived animals relative to controls (sublaterodorsal nucleus: 85.0 ± 15.5 cells vs. 23.0 ± 1.2, P = 0.004; ventrolateral periaqueductal gray: 652.8 ± 71.7 cells vs. 889.3 ± 66.8, P = 0.042). CONCLUSIONS: In rodents recovering from sevoflurane, REM-on and REM-off neuronal activity maps closely resemble those of REM sleep-deprived animals. These findings provide new evidence in support of the idea that sevoflurane does not substitute for endogenous REM sleep.
Assuntos
Roedores , Sono REM , Animais , Camundongos , Ratos , Eletroencefalografia , Proteínas Proto-Oncogênicas c-fos , Roedores/metabolismo , Sevoflurano , Sono/fisiologia , Privação do Sono/metabolismo , Sono REM/fisiologiaRESUMO
INTRODUCTION: Despite resuscitation advances including extracorporeal cardiopulmonary resuscitation (ECPR), freedom from neurologic and myocardial insult after cardiac arrest remains unlikely. We hypothesized that adenosine 2A receptor (A2AR) agonism, which attenuates reperfusion injury, would improve outcomes in a porcine model of ECPR. METHODS: Adult swine underwent 20 min of circulatory arrest followed by defibrillation and 6 h of ECPR. Animals were randomized to receive saline vehicle or A2AR agonist (ATL1223 or Regadenoson) infusion during extracorporeal membrane oxygenation. Animals were weaned off extracorporeal membrane oxygenation and monitored for 24 h. Clinical and biochemical end points were compared. RESULTS: The administration of A2AR agonists increased survival (P = 0.01) after cardiac arrest compared to vehicle. Markers of neurologic damage including S100 calcium binding protein B and glial fibrillary acidic protein were significantly lower with A2AR agonist treatment. CONCLUSIONS: In a model of cardiac arrest treated with ECPR, A2AR agonism increased survival at 24 h and reduced neurologic damage suggesting A2AR activation may be a promising therapeutic target after cardiac arrest.
RESUMO
BACKGROUND: We aimed to further validate our previously published animal model for delirium by testing the hypothesis that in aged mice, Anesthesia, Surgery and simulated ICU conditions (ASI) induce sleep fragmentation, electroencephalographic (EEG) slowing, and circadian disarray consistent with intensive care unit (ICU) patients with delirium. METHODS: A total of 41 mice were used. Mice were implanted with EEG electrodes and randomized to ASI or control groups. ASI mice received laparotomy, anesthesia, and simulated ICU conditions. Controls did not receive ASI. Sleep was recorded at the end of ICU conditions, and hippocampal tissue was collected on EEG recording. Arousals, EEG dynamics, and circadian gene expression were compared with t tests. Two-way repeated measures analysis of variance (RM ANOVA) was used to assess sleep according to light. RESULTS: ASI mice experienced frequent arousals (36.6 ± 3.2 vs 26.5 ± 3.4; P = .044; 95% confidence interval [CI], 0.29-19.79; difference in mean ± SEM, 10.04 ± 4.62) and EEG slowing (frontal theta ratio, 0.223 ± 0.010 vs 0.272 ± 0.019; P = .026; 95% CI, -0.091 to -0.007; difference in mean ± SEM, -0.05 ± 0.02) relative to controls. In ASI mice with low theta ratio, EEG slowing was associated with a higher percentage of quiet wakefulness (38.2 ± 3.6 vs 13.4 ± 3.8; P = .0002; 95% CI, -35.87 to -13.84; difference in mean ± SEM, -24.86 ± 5.19). ASI mice slept longer during the dark phases of the circadian cycle (nonrapid eye movement [NREM], dark phase 1 [D1]: 138.9 ± 8.1 minutes vs 79.6 ± 9.6 minutes, P = .0003, 95% CI, -95.87 to -22.69, predicted mean difference ± SE: -59.28 ± 13.89; NREM, dark phase 2 (D2): 159.3 ± 7.3 minutes vs 112.6 ± 15.5 minutes, P = .006, 95% CI, -83.25 to -10.07, mean difference ± SE, -46.66 ± 13.89; rapid eye movement (REM), D1: 20.5 ± 2.1 minutes vs 5.8 ± 0.8 minutes, P = .001, 95% CI, -24.60 to -4.71, mean difference ± SE, -14. 65 ± 3.77; REM, D2: 21.0 ± 2.2 minutes vs 10.3 ± 1.4 minutes, P = .029, 95% CI, -20.64 to -0.76, mean difference ± SE, -10.70 ± 3.77). The expression of essential circadian genes was also lower in ASI mice (basic helix-loop-helix ARNT like [BMAL1] : -1.3 fold change; circadian locomotor output cycles protein kaput [CLOCK] : -1.2). CONCLUSIONS: ASI mice experienced EEG and circadian changes mimicking those of delirious ICU patients. These findings support further exploration of this mouse approach to characterize the neurobiology of delirium.
Assuntos
Delírio , Privação do Sono , Animais , Camundongos , Ritmo Circadiano , Delírio/diagnóstico , Eletroencefalografia , Unidades de Terapia Intensiva , SonoRESUMO
OBJECTIVES: The aim was to characterize hospitalization costs, charges, and lengths of hospital stay for COVID-19 patients treated with venovenous (VV) extracorporeal membrane oxygenation (ECMO) in the United States during 2020. Secondarily, differences in hospitalization costs, charges, and lengths of hospital stay were explored based on hospital-level factors. DESIGN: Retrospective cohort study. SETTING: Multiple hospitals in the United States. PARTICIPANTS: Adult patients with COVID-19 who were on VV ECMO in 2020 and had data in the national inpatient sample. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics and baseline comorbidities were recorded for patients. Primary study outcomes were hospitalization costs, charges, and lengths of hospital stay. Study outcomes were compared after stratification by hospital region, bed size, and for-profit status. The median hospitalization cost for the 3,315-patient weighted cohort was $200,300 ($99,623, $338,062). Median hospitalization charges were $870,513 ($438,228, $1,553,157), and the median length of hospital stay was 30 days (17, 46). Survival to discharge was 54.4% for all patients in the cohort. Median hospitalization cost differed by region (p = 0.01), bed size (p < 0.001), and for-profit status (p = 0.02). Median hospitalization charges also differed by region (p = 0.04), bed size (p = 0.002), and for-profit status (p < 0.001). Length of hospital stay differed by region (p = 0.03) and bed size (p < 0.001), but not for-profit status (p = 0.40). Hospitalization costs were the lowest, and charges were highest in private-for-profit hospitals. Large hospitals also had higher costs, charges, and hospital stay lengths than small hospitals. CONCLUSIONS: In this retrospective cohort study, hospitalization costs and charges for patients with COVID-19 on VV ECMO were found to be substantial but similar to what has been reported previously for patients without COVID-19 on VV ECMO. Significant variation was observed in costs, charges, and lengths of hospital stay based on hospital-level factors.
Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Adulto , Humanos , Estados Unidos/epidemiologia , Tempo de Internação , Estudos de Coortes , Estudos Retrospectivos , COVID-19/terapia , HospitalizaçãoRESUMO
Delirium is a common, morbid, and costly syndrome that is closely linked to Alzheimer's disease (AD) and AD-related dementias (ADRD) as a risk factor and outcome. Human studies of delirium have advanced our knowledge of delirium incidence and prevalence, risk factors, biomarkers, outcomes, prevention, and management. However, understanding of delirium neurobiology remains limited. Preclinical and translational models for delirium, while challenging to develop, could advance our knowledge of delirium neurobiology and inform the development of new prevention and treatment approaches. We discuss the use of preclinical and translational animal models in delirium, focusing on (1) a review of current animal models, (2) challenges and strategies for replicating elements of human delirium in animals, and (3) the utility of biofluid, neurophysiology, and neuroimaging translational markers in animals. We conclude with recommendations for the development and validation of preclinical and translational models for delirium, with the goal of advancing awareness in this important field.
Assuntos
Doença de Alzheimer , Delírio , Animais , Humanos , Doença de Alzheimer/complicações , Fatores de Risco , Neuroimagem , Incidência , Delírio/epidemiologiaRESUMO
BACKGROUND: Previous studies suggest that rapid eye movement sleep rebound and disruption of rapid eye movement sleep architecture occur during the first 24 h after general anesthesia with volatile anesthetics in adult rats. However, it is unknown whether rapid eye movement sleep alterations persist beyond the anesthetic recovery phase in neonatal rats. This study tested the hypothesis that rapid eye movement sleep disturbances would be present in adolescent rats treated with anesthesia on postnatal day 7. METHODS: Forty-four neonatal rats were randomly allocated to treatment with anesthesia consisting of midazolam, nitrous oxide, and isoflurane or control conditions for 2 h or 6 h. Electroencephalographic and electromyographic electrodes were implanted and recordings obtained between postnatal days 26 and 34. The primary outcome was time spent in rapid eye movement sleep. Data were analyzed using two-tailed unpaired t tests and two-way repeated measures analysis of variance. RESULTS: Rats treated with midazolam, nitrous oxide, and isoflurane exhibited a significant increase in rapid eye movement sleep three weeks later when compared with control rats, regardless of whether they were treated for 2 h (174.0 ± 7.2 min in anesthetized, 108.6 ± 5.3 in controls, P < 0.0001) or 6 h (151.6 ± 9.9 min in anesthetized, 108.8 ± 7.1 in controls, P = 0.002). CONCLUSIONS: Treatment with midazolam, nitrous oxide, and isoflurane on postnatal day 7 increases rapid eye movement sleep three weeks later in rats.
Assuntos
Anestesia Geral/tendências , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Homeostase/efeitos dos fármacos , Sono REM/efeitos dos fármacos , Anestesia Geral/efeitos adversos , Anestésicos Inalatórios/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Animais , Animais Recém-Nascidos , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Feminino , Homeostase/fisiologia , Isoflurano/administração & dosagem , Isoflurano/efeitos adversos , Masculino , Midazolam/administração & dosagem , Midazolam/efeitos adversos , Óxido Nitroso/administração & dosagem , Óxido Nitroso/efeitos adversos , Ratos , Ratos Sprague-Dawley , Sono REM/fisiologiaRESUMO
Prevailing literature supports the idea that common general anesthetics (GAs) cause long-term cognitive changes and neurodegeneration in the developing mammalian brain, especially in the thalamus. However, the possible role of GAs in modifying ion channels that control neuronal excitability has not been taken into consideration. Here we show that rats exposed to GAs at postnatal day 7 display a lasting reduction in inhibitory synaptic transmission, an increase in excitatory synaptic transmission, and concomitant increase in the amplitude of T-type calcium currents (T-currents) in neurons of the nucleus reticularis thalami (nRT). Collectively, this plasticity of ionic currents leads to increased action potential firing in vitro and increased strength of pharmacologically induced spike and wave discharges in vivo. Selective blockade of T-currents reversed neuronal hyperexcitability in vitro and in vivo. We conclude that drugs that regulate thalamic excitability may improve the safety of GAs used during early brain development.
Assuntos
Anestesia Geral , Córtex Cerebral , Vias Neurais/fisiologia , Tálamo , 4-Butirolactona/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Benzamidas/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Feminino , Técnicas In Vitro , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Masculino , Vias Neurais/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Piperidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Tálamo/citologia , Tálamo/efeitos dos fármacos , Tálamo/crescimento & desenvolvimentoRESUMO
Serotonin syndrome (SS) is a life-threatening condition caused by serotonergic medications. We describe a unique case of SS likely caused by prolonged exposure to propofol and remifentanil alone. A young male presented for vestibular schwannoma resection. Several hours into the case, the patient demonstrated hyperthermia and hemodynamic instability, followed by clonus, rigidity, shivering, and tachycardia after emergence. SS was diagnosed using Hunter's criteria and improved with supportive measures. While the patient endorsed a history of methamphetamine use, his urine drug screen was negative. The possibility of SS should be considered when administering propofol and remifentanil, particularly with prolonged infusions.
Assuntos
Craniotomia , Propofol , Remifentanil , Síndrome da Serotonina , Humanos , Remifentanil/efeitos adversos , Remifentanil/administração & dosagem , Masculino , Propofol/efeitos adversos , Propofol/administração & dosagem , Síndrome da Serotonina/induzido quimicamente , Craniotomia/efeitos adversos , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/administração & dosagem , Adulto , Infusões Intravenosas , Neuroma Acústico/cirurgia , Piperidinas/efeitos adversos , Piperidinas/administração & dosagemRESUMO
BACKGROUND: Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. In vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events. METHODS: Because proper and timely mitochondrial morphogenesis is critical for brain development, the authors examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups. RESULTS: This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (more than 30%, P < 0.05), impairment of their structural integrity, an approximately 28% increase in their complex IV activity (P < 0.05), and a twofold decrease in their regional distribution in presynaptic neuronal profiles (P < 0.05), where their presence is important for the normal development and functioning of synapses. Consequently, the authors showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (approximately 27%, P < 0.05), and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established. CONCLUSION: Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration.
Assuntos
Anestésicos Gerais/toxicidade , Encéfalo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Anestesia Geral/efeitos adversos , Animais , Encéfalo/embriologia , Mitocôndrias/ultraestrutura , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To establish a clinically relevant mouse model of perioperative delirium. METHODS: Aged C57BL/6J mice were tested at baseline in the Y-maze novel arm preference, buried food, simple discrimination task of the attentional set-shifting test, and open field tests. They were subsequently randomized to insult (anesthesia, surgery, and Intensive Care Unit environment) or control group. Insult-exposed mice received laparotomy under sevoflurane anesthesia, propofol sedation and exposure to intermittent lights, sounds and cage shaking. Controls did not receive anesthesia, surgery, or intensive care environment. All mice were tested in the Y-maze novel arm preference, buried food, attentional, and open field tests at the end of intensive care environment (0 h) and every 6 h up to 24 h. Mouse hippocampi were collected at 24 h for gene expression analyses. RESULTS: Surgery, anesthesia and Intensive Care environment decreased the entries in the Y-maze novel arm at 0 h (P = 0.001), 6 h (P < 0.001), 18 h (P = 0.002), and 24 h (P = 0.029). Insult exposure increased the latency to find a buried cereal reward at 18 h (P = 0.035) and 24 h (P = 0.027), and increased the trials to criterion in the reverse compound discrimination (P = 0.013) and extradimensional shift (P < 0.001) tasks of the attentional test. The overall incidence of delirium was 72% in A/S/I mice. Messenger RNA levels of synuclein alpha (-3.785 fold change relative to controls), Neurotrophic Receptor Tyrosine Kinase1 (-2.267), and syntaxin1a (-1.498) were decreased in the hippocampus of mice 24 h after insult exposure. Protein levels of syntaxin 1a (P = 0.012), Neurotrophic Receptor Tyrosine Kinase1 (P = 0.039), synuclein alpha (P = 0.017), phosphorylated synuclein alpha (P = 0.008), synaptophysin (P = 0.002), postsynaptic density protein 95 (P = 0.003), and microtubule-associated protein 2 (P = 0.013) were also decreased, relative to controls. CONCLUSION: Surgery, anesthesia and Intensive Care environment impaired mouse behaviors that depend on attention, memory, and thought organization. The changes were acute in onset and fluctuating in time. Mice with delirium exhibited decreased expression of key synaptic function-related genes. The behavioral changes induced by anesthesia, surgery, and Intensive Care environment in aged mice are consistent with the clinical features of human delirium, and support the use of this animal model for future mechanistic studies of perioperative delirium.
RESUMO
The age of modern medicine has ushered in remarkable advances and with them increased longevity of life. The questions are, however: Has everyone benefited from these developments equally? and Do all lives truly matter? The presence of gender and racial health disparities indicates that there is work still left to be done. The first target of intervention may well be the medical establishment itself. The literature presented in this article identifies potential targets for interventions and future areas of exploration.
Assuntos
Cuidados Críticos , Disparidades em Assistência à Saúde/etnologia , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Papel do Médico , Medicina de Precisão , Caracteres SexuaisRESUMO
The influence of historical cultural norms is evident when analyzing the physician demographics in the United States. To this day, there exists a paucity in diversity as it pertains to gender balance and ethnicity. This phenomenon is particularly concerning when studies support the notion that race and gender concordance are associated with improved outcomes. The literature presented in this article identifies potential targets for interventions on how to attract, train, and retain minority physicians.
Assuntos
Médicas/estatística & dados numéricos , Médicos/estatística & dados numéricos , Recursos Humanos/estatística & dados numéricos , Serviços de Saúde Comunitária , Cuidados Críticos , Humanos , Liderança , Grupos MinoritáriosRESUMO
Our laboratory and many others have exploited the high resolving power of transmission electron microscopy to study the morphology and spatial organization of synaptic vesicles. In order to obtain high-quality electron micrographs that can yield the degree of morphological detail necessary for quantitative analysis of pre-synaptic vesicle distribution, optimal specimen preparation is critical. Chemical fixation is the first step in the process of specimen preparation, and of utmost importance to preserve fine ultrastructure. Vascular fixation with a glutaraldehyde-formaldehyde solution, followed by treatment of vibratome-sectioned specimens with osmium tetroxide, stabilizes the maximum number of molecules, especially proteins and lipids, and results in superior conservation of ultrastructure. Tissue is then processed with counterstaining, sequential dehydration and resin-embedding. En bloc staining with uranyl acetate (i.e., staining of vibratome-sectioned tissue before resin embedding) enhances endogenous contrast and stabilizes cell components against extraction during specimen processing. Contrast can be further increased by applying uranyl acetate as a post-stain on ultrathin sections. Double-staining of ultrathin sections with lead citrate after uranyl acetate treatment also improves image resolution, by intensifying electron-opacity of nucleic acid-containing structures through selective binding of lead to uranyl acetate. Transmission electron microscopy is a powerful tool for characterization of the morphological details of synaptic vesicles and quantification of their size and spatial organization in the terminal bouton. However, because it uses fixed tissue, transmission electron microscopy can only provide indirect information regarding living or evolving processes. Therefore, other techniques should be considered when the main objective is to study dynamic or functional aspects of synaptic vesicle trafficking and exocytosis.
Assuntos
Encéfalo/citologia , Técnicas Citológicas/métodos , Terminações Nervosas/ultraestrutura , Vesículas Sinápticas/metabolismo , Vesículas Sinápticas/ultraestrutura , Animais , Animais Recém-Nascidos , Microscopia Eletrônica de Transmissão , Ratos , Manejo de EspécimesRESUMO
Early exposure to anesthetics may interfere with synaptic development and lead to cognitive deficits. We previously demonstrated a decrease in vesicles docked at and within 100 nm from the presynaptic membrane in hippocampal nerve terminals of neonatal rats after anesthesia. Hence, we designed this study to assess the effects of neonatal anesthesia on synapsin 1 (Syn1) and synaptotagmin 1 (Syt1), two key regulators of vesicle docking and fusion. To test the link between changes in Syn1 and Syt1 and behavioral deficits observed after neonatal anesthesia, we also assessed retention memory and fear conditioning in adolescent rats after neonatal anesthesia. Pups received a combination of clinical anesthetics, then Syn1 and Syt1 mRNA and protein expression were determined at the peak (postnatal day 8, P8), part-way through (P12) and end of synaptogenesis (P24) in the CA1-subiculum by qPCR and western blotting. Anesthesia decreased Syn1 and Syt1 mRNA expression at P8 (P<0.01 and <0.001) and P12 (P=0.001 and 0.017), but not P24 (P=0.538 and 0.671), and impaired Syn1, p-Syn1, and Syt1 protein levels at P8 (P=0.038, 0.041, and 0.004, respectively), P12 (P<0.001, P=0.001, and P<0.0001), and P24 (P=0.025, 0.031, and 0.001). Anesthetic-challenged rats displayed deficient long-term retention memory (P=0.019) and hippocampus-dependent fear conditioning (P<0.001). These results suggest that anesthetics alter Syn1 and Syt1 during synapse assembly and maturation, raising the possibility that anesthetic interference with Syn1 and Syt1 could initiate changes in synaptic function that contribute to the cognitive deficits observed after neonatal anesthesia.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Região CA1 Hipocampal/efeitos dos fármacos , Isoflurano/administração & dosagem , Sinapsinas/metabolismo , Vesículas Sinápticas/efeitos dos fármacos , Sinaptotagmina I/metabolismo , Animais , Animais Recém-Nascidos , Região CA1 Hipocampal/metabolismo , Feminino , Masculino , Ratos Sprague-Dawley , Memória Espacial/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Vesículas Sinápticas/metabolismoRESUMO
We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS.
RESUMO
AIM: To evaluate the possible correlation between the respiratory pattern in determining the craniofacial dimensions, using as baseline the Tweed-Merrifields cephalometric analysis, added to angle SN-GoGn and to Y axis angle. METHODOLOGY: The selected sample to this study comprised 50 teleradiographies taken in lateral and natural positions of the head in young female patients at the age of 9 to 12 years, presenting mean age of 10 years and 5 months and Class 1 malocclusion. After diagnosis of respiratory pattern, the sample was divided into two groups: control group, 25 teleradiographies of nasal breathers in lateral and natural positions of the head; experimental group, 25 teleradiographies of predominantly mouth breathers in lateral and natural positions of the head. RESULTS: The results were submitted to descriptive analysis (mean and standard deviation), test F and "t" Student test with significance level of 5%. There was no significant difference between the group with nasal breathing and the group with predominantly mouth breathing for any of the studied variables.
Assuntos
Cefalometria , Ossos Faciais/diagnóstico por imagem , Respiração Bucal/fisiopatologia , Mecânica Respiratória/fisiologia , Criança , Ossos Faciais/fisiopatologia , Feminino , Humanos , RadiografiaRESUMO
Recent evidence supports the idea that common general anesthetics (GAs) such as isoflurane (Iso) and nitrous oxide (N2O; laughing gas) are neurotoxic and may harm the developing mammalian brain, including the thalamus; however, to date very little is known about how developmental exposure to GAs may affect synaptic transmission in the thalamus which, in turn, controls the function of thalamocortical circuitry. To address this issue we used in vitro patch-clamp recordings of evoked inhibitory postsynaptic currents (eIPSCs) from intact neurons of the nucleus reticularis thalami (nRT) in brain slices from rat pups (postnatal age P10-P18) exposed at age of P7 to clinically relevant GA combinations of Iso and N2O. We found that rats exposed to a combination of 0.75 % Iso and 75 % N2O display lasting reduction in the amplitude and faster decays of eIPSCs. Exposure to sub-anesthetic concentrations of 75 % N2O alone or 0.75 % Iso alone at P7 did not affect the amplitude of eIPSCs; however, Iso alone, but not N2O, significantly accelerated decay of eIPSCs. Anesthesia with 1.5 % Iso alone decreased amplitudes, caused faster decay and decreased the paired-pulse ratio of eIPSCs. We conclude that anesthesia at P7 with Iso alone or in combination with N2O causes plasticity of eIPSCs in nRT neurons by both presynaptic and postsynaptic mechanisms. We hypothesize that changes in inhibitory synaptic transmission in the thalamus induced by GAs may contribute to altered neuronal excitability and consequently abnormal thalamocortical oscillations later in life.
Assuntos
Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/toxicidade , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Isoflurano/toxicidade , Terminações Pré-Sinápticas/efeitos dos fármacos , Vesículas Sinápticas/efeitos dos fármacos , Núcleos Ventrais do Tálamo/efeitos dos fármacos , Anestésicos Inalatórios/administração & dosagem , Animais , Transporte Biológico/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Sinergismo Farmacológico , Estimulação Elétrica , Feminino , Isoflurano/administração & dosagem , Masculino , Microscopia Eletrônica , Midazolam/administração & dosagem , Midazolam/toxicidade , Degeneração Neural/induzido quimicamente , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Óxido Nitroso/administração & dosagem , Óxido Nitroso/toxicidade , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/ultraestrutura , Ratos , Ratos Sprague-Dawley , Vesículas Sinápticas/ultraestrutura , Núcleos Ventrais do Tálamo/crescimento & desenvolvimento , Núcleos Ventrais do Tálamo/ultraestruturaRESUMO
UNLABELLED: Aware of the diffusion capacity of bleaching in the dental tissues, many orthodontists are subjecting their patients to dental bleaching during orthodontic treatment for esthetic purposes or to anticipate the exchange of esthetic restorations after the orthodontic treatment. For this purpose specific products have been developed in pre-loaded whitening trays designed to fit over and around brackets and wires, with clinical efficacy proven. OBJECTIVE: The objective of this study was to evaluate, through spectrophotometric reflectance, the effectiveness of dental bleaching under orthodontic bracket. MATERIAL AND METHODS: Thirty-two bovine incisors crown blocks of 8 mm x 8 mm height lengths were used. Staining of tooth blocks with black tea was performed for six days. They were distributed randomly into 4 groups (1-home bleaching with bracket, 2- home bleaching without bracket, 3- office bleaching with bracket, 4 office bleaching without bracket). The color evaluation was performed (CIE L * a * b *) using color reflectance spectrophotometer. Metal brackets were bonded in groups 1 and 3. The groups 1 and 2 samples were subjected to the carbamide peroxide at 15%, 4 hours daily for 21 days. Groups 3 and 4 were subjected to 3 in-office bleaching treatment sessions, hydrogen peroxide 38%. After removal of the brackets, the second color evaluation was performed in tooth block, difference between the area under the bracket and around it, and after 7 days to verified color stability. Data analysis was performed using the paired t-test and two-way variance analysis and Tukey's. RESULTS: The home bleaching technique proved to be more effective compared to the office bleaching. There was a significant difference between the margin and center color values of the specimens that were subjected to bracket bonding. CONCLUSIONS: The bracket bond presence affected the effectiveness of both the home and office bleaching treatments. Key words:Tooth bleaching, spectrophotometry, orthodontics.