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This study reports the development of a photocatalytic electrochemical aptasensor for the purpose of detecting chloramphenicol (CAP) antibiotic residues in water by utilizing SYBR Green I (SG) and chemically exfoliated MoS2 (ce-MoS2) as synergistically signal-amplification platforms. The Au nanoparticles (AuNPs) were electrodeposited onto the surface of an indium tin oxide (ITO) electrode. After that, the thiolate-modified cDNA, also known as capture DNA, was combined with the aptamer. Subsequently, photosensitized SG molecules and ce-MoS2 nanomaterial were inserted into the groove of the resultant double-stranded DNA (dsDNA). The activation of the photocatalytic process upon exposure to light resulted in the generation of singlet oxygen. The singlet oxygen effectively split the dsDNA, resulting in significant enhancement in the current of [Fe(CN)6]3-/4-. When the CAP was present, both SG molecules and ce-MoS2 broke away from the dsDNA, which turned off the photosensitization response, leading to significant reduction in the current of [Fe(CN)6]3-/4-. Under the optimal conditions, the aptasensor exhibited a linear relationship between the current of [Fe(CN)6]3-/4- with logarithmic concentrations of CAP from 20 to 1000 nM, with a detection of limit (3σ) of 3.391 nM. The aptasensor also demonstrated good selectivity towards CAP in the presence of interfering antibiotics, such as tetracycline, streptomycin, levofloxacin, ciprofloxacin, and sulfadimethoxine. Additionally, the results obtained from the analysis of natural water samples using the proposed aptasensor were consistent with the findings acquired through the use of a liquid chromatograph-mass spectrometer. Therefore, with its simplicity and high selectivity, this aptasensor can potentially detect alternative antibiotics in environmental water samples by replacing the aptamers based on photosensitization.
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Aptámeros de Nucleótidos , Benzotiazoles , Técnicas Biosensibles , Cloranfenicol , Diaminas , Disulfuros , Técnicas Electroquímicas , Molibdeno , Compuestos Orgánicos , Quinolinas , Cloranfenicol/análisis , Aptámeros de Nucleótidos/química , Técnicas Electroquímicas/métodos , Molibdeno/química , Diaminas/química , Disulfuros/química , Benzotiazoles/química , Quinolinas/química , Compuestos Orgánicos/química , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , Oro/química , Fármacos Fotosensibilizantes/química , Antibacterianos/análisis , Límite de Detección , Contaminantes Químicos del Agua/análisis , Procesos Fotoquímicos , Tamaño de la PartículaRESUMEN
Background: Dexmedetomidine has been used as a perineural local anesthetic (LA) adjuvant to facilitate the potency of erector spinal plane block (ESPB). This quantitative review aimed to evaluate whether perineural dexmedetomidine for ESPB can improve the effects of analgesia compared to LA alone. Methods: Randomized controlled trials (RCTs) that investigated the addition of dexmedetomidine to LA compared to LA alone in ESPB were included. The pain scores, duration of sensory block, the time to first analgesia requirement, postoperative morphine consumption, rescue analgesia, and dexmedetomidine-related side effects were analyzed and combined using random-effects models. Results: A total of 823 patients from 13 RCTs were analyzed. Dexmedetomidine was used at the concentration of 0.5 µg/kg in three trials and 1 µg/kg in nine trials, and both in one trial. Both concentrations of dexmedetomidine perineurally administrated significantly reduced the rest VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.86; 95% CI: -1.59 to -0.12; p = 0.02; 1 µg/kg dexmedetomidine: MD = -0.49; 95% CI: -0.83 to -0.16; p = 0.004), and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.43; 95% CI: -0.74 to -0.13; p = 0.005; 1 µg/kg dexmedetomidine: MD = -0.62; 95% CI: -0.84 to -0.41; p < 0.00001). Both concentrations of dexmedetomidine added in LAs improved the dynamic VAS scores postoperatively at 12 h (0.5 µg/kg dexmedetomidine: MD = -0.55; 95% CI: -0.95 to -0.15; p = 0.007; 1 µg/kg dexmedetomidine: MD = -0.66; 95% CI: -1.05 to -0.28; p = 0.0006) and 24 h (0.5 µg/kg dexmedetomidine: MD = -0.52; 95% CI: -0.94 to -0.10; p = 0.01; 1 µg/kg dexmedetomidine: MD = -0.46; 95% CI: -0.75 to -0.16; p = 0.002). Furthermore, perineural dexmedetomidine prolonged the duration of the sensory block and the time to first analgesia requirement, reduced postoperative morphine consumption, and lowered the incidence of rescue analgesia and chronic pain. Conclusion: The meta-analysis showed that using perineural dexmedetomidine at either 0.5 µg/kg or 1 µg/kg doses in ESPB can effectively and safely enhance pain relief. Systematic review registration: PROSPERO (CRD42023424532: https://www.crd.york.ac.uk/PROSPERO/).
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Toxinas Botulínicas Tipo A , Humanos , Toxinas Botulínicas Tipo A/administración & dosificación , Dolor en Cáncer/tratamiento farmacológico , Metaanálisis como Asunto , Neoplasias/tratamiento farmacológico , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/efectos adversos , Manejo del Dolor/métodos , Revisiones Sistemáticas como AsuntoAsunto(s)
Equinococosis , Humanos , Equinococosis/cirugía , Equinococosis/diagnóstico por imagen , Hipertensión Intracraneal/cirugía , Hipertensión Intracraneal/etiología , Masculino , Complicaciones Intraoperatorias/etiología , Encefalopatías/cirugía , Encefalopatías/parasitología , Encefalopatías/diagnóstico por imagen , Adulto , Presión Intracraneal , FemeninoRESUMEN
Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically necessary pharmacological effects, respiratory depression is a critical side effect induced by most general anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is important for the development of safer general anesthetics. Currently used volatile anesthetics and most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics produce differential effects on respiratory characteristics, including the respiratory rate, tidal volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms underlying anesthetic-induced breathing depression mainly include modulation of synaptic transmission of ligand-gated ionotropic receptors (e.g., γ-aminobutyric acid, N-methyl-D-aspartate, and nicotinic acetylcholine receptors) and ion channels (e.g., voltage-gated sodium, calcium, and potassium channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively summarizes the modulation of the respiratory system by clinically used general anesthetics, including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics, such as opioids, which cause respiratory depression and the "opioid crisis", are discussed. Finally, underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are summarized.
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Anestésicos Generales , Receptores Nicotínicos , Insuficiencia Respiratoria , Animales , Humanos , Anestésicos Generales/farmacología , Anestésicos Generales/uso terapéutico , Analgésicos , Sistema Nervioso , Canales de Potasio , Sodio , MamíferosRESUMEN
Background: How volatile anesthetics work remains poorly understood. Modulations of synaptic neurotransmission are the direct cellular mechanisms of volatile anesthetics in the central nervous system. Volatile anesthetics such as isoflurane may reduce neuronal interaction by differentially inhibiting neurotransmission between GABAergic and glutamatergic synapses. Presynaptic voltage-dependent sodium channels (Nav), which are strictly coupled with synaptic vesicle exocytosis, are inhibited by volatile anesthetics and may contribute to the selectivity of isoflurane between GABAergic and glutamatergic synapses. However, it is still unknown how isoflurane at clinical concentrations differentially modulates Nav currents between excitatory and inhibitory neurons at the tissue level. Methods: In this study, an electrophysiological recording was applied in cortex slices to investigate the effects of isoflurane on Nav between parvalbumin (PV+) and pyramidal neurons in PV-cre-tdTomato and/or vglut2-cre-tdTomato mice. Results: Isoflurane at clinically relevant concentrations produced a hyperpolarizing shift in the voltage-dependent inactivation and slowed the recovery time from the fast inactivation in both cellular subtypes. Since the voltage of half-maximal inactivation was significantly depolarized in PV+ neurons compared to that of pyramidal neurons, isoflurane inhibited the peak Nav currents in pyramidal neurons more potently than those of PV+ neurons (35.95 ± 13.32% vs. 19.24 ± 16.04%, P = 0.036 by the Mann-Whitney test). Conclusions: Isoflurane differentially inhibits Nav currents between pyramidal and PV+ neurons in the prefrontal cortex, which may contribute to the preferential suppression of glutamate release over GABA release, resulting in the net depression of excitatory-inhibitory circuits in the prefrontal cortex.
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Anestésicos por Inhalación , Isoflurano , Canales de Sodio Activados por Voltaje , Ratones , Animales , Isoflurano/farmacología , Parvalbúminas , Anestésicos por Inhalación/farmacología , Neuronas , Células Piramidales/fisiología , Corteza PrefrontalRESUMEN
Astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain, but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.1) is the most important background K+ channel in astrocytes. However, how Kir4.1 is regulated and contributes to behavioral hyperalgesia in chronic pain is unknown. In this study, single-cell RNA sequencing analysis indicated that the expression levels of both Kir4.1 and Methyl-CpG-binding protein 2 (MeCP2) were decreased in spinal astrocytes after chronic constriction injury (CCI) in a mouse model. Conditional knockout of the Kir4.1 channel in spinal astrocytes led to hyperalgesia, and overexpression of the Kir4.1 channel in spinal cord relieved CCI-induced hyperalgesia. Expression of spinal Kir4.1 after CCI was regulated by MeCP2. Electrophysiological recording in spinal slices showed that knockdown of Kir4.1 significantly up-regulated the excitability of astrocytes and then functionally changed the firing patterns of neurons in dorsal spinal cord. Therefore, targeting spinal Kir4.1 may be a therapeutic approach for hyperalgesia in chronic neuropathic pain.
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Astrocitos , Neuralgia , Animales , Ratones , Astrocitos/metabolismo , Hiperalgesia/metabolismo , Proteína 2 de Unión a Metil-CpG/genética , Neuralgia/genética , Médula Espinal/metabolismo , Asta Dorsal de la Médula EspinalRESUMEN
BACKGROUND: The dentate gyrus (DG) has been implicated in the pathophysiology of depression. Many studies have revealed the cellular types, neural circuits, and morphological changes of the DG involved in the development of depression. However, the molecular regulating its intrinsic activity in depression is unknown. METHODS: Utilizing the mode of depression induced by lipopolysaccharide (LPS), we investigate the involvement of the sodium leak channel (NALCN) in inflammation-induced depressive-like behaviors of male mice. The expression of NALCN was detected by immunohistochemistry and real-time polymerase chain reaction. DG microinjection of the adeno-associated virus or lentivirus was carried out using a stereotaxic instrument and followed by behavioral tests. Neuronal excitability and NALCN conductance were recorded by whole-cell patch-clamp techniques. RESULTS: The expression and function of NALCN were reduced in both the dorsal and ventral DG in LPS-treated mice; whereas, only knocking down NALCN in the ventral pole produced depressive-like behaviors and this effect of NALCN was specific to ventral glutamatergic neurons. The excitability of ventral glutamatergic neurons was impaired by both the knockdown of NALCN and/or the treatment of LPS. Then, the overexpression of NALCN in the ventral glutamatergic neurons decreased the susceptibility of mice to inflammation-induced depression, and the intracranial injection of substance P (non-selective NALCN activator) into the ventral DG rapidly ameliorated inflammation-induced depression-like behaviors in an NALCN-dependent manner. CONCLUSIONS: NALCN, which drives the neuronal activity of the ventral DG glutamatergic neurons, uniquely regulates depressive-like behaviors and susceptibility to depression. Therefore, the NALCN of glutamatergic neurons in the ventral DG may present a molecular target for rapid antidepressant drugs.
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Giro Dentado , Depresión , Canales Iónicos , Lipopolisacáridos , Animales , Masculino , Ratones , Giro Dentado/metabolismo , Giro Dentado/patología , Depresión/genética , Depresión/metabolismo , Ácido Glutámico/metabolismo , Inflamación/complicaciones , Canales Iónicos/metabolismo , Lipopolisacáridos/farmacología , Proteínas de la Membrana/metabolismo , Neuronas/metabolismo , Sodio/metabolismoRESUMEN
BACKGROUND: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl- co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development. METHODS: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg-1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift. RESULTS: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1ß) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1ß mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1ß or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation. CONCLUSIONS: Sustained elevation of IL-1ß in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.
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Disfunción Cognitiva , Simportadores , Animales , Disfunción Cognitiva/inducido químicamente , Hipocampo/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolisacáridos , Ratas , Simportadores/genética , Simportadores/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Cotransportadores de K ClRESUMEN
Background: Electroencephalography (EEG) recordings under propofol exhibit an increase in slow and alpha oscillation power and dose-dependent phase-amplitude coupling (PAC), which underlie GABAA potentiation and the central role of thalamocortical entrainment. However, the exact EEG signatures elicited by volatile anesthetics and the possible neurophysiological mechanisms remain unclear. Methods: Cortical EEG signals and thalamic local field potential (LFP) were recorded in a mouse model to detect EEG signatures induced by 0.9%, 1.5%, and 2.0% isoflurane. Then, the power of the EEG spectrum, thalamocortical coherence, and slow-alpha phase-amplitude coupling were analyzed. A computational model based on the thalamic network was used to determine the primary neurophysiological mechanisms of alpha spiking of thalamocortical neurons under isoflurane anesthesia. Results: Isoflurane at 0.9% (light anesthesia) increased the power of slow and delta oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 1.5% (surgery anesthesia) increased the power of alpha oscillations both in cortical EEG and in thalamic LFP. Isoflurane at 2% (deep anesthesia) further increased the power of cortical alpha oscillations, while thalamic alpha oscillations were unchanged. Thalamocortical coherence of alpha oscillation only exhibited a significant increase under 1.5% isoflurane. Isoflurane-induced PAC modulation remained unchanged throughout under various concentrations of isoflurane. By adjusting the parameters in the computational model, isoflurane-induced alpha spiking in thalamocortical neurons was simulated, which revealed the potential molecular targets and the thalamic network involved in isoflurane-induced alpha spiking in thalamocortical neurons. Conclusion: The EEG changes in the cortical alpha oscillation, thalamocortical coherence, and slow-alpha PAC may provide neurophysiological signatures for monitoring isoflurane anesthesia at various depths.
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Background: Volatile anesthetics including sevoflurane and isoflurane enhance oscillations of cortical electroencephalogram (EEG), partly by their modulations on glutamate-mediated excitatory synaptic transmission. Expression of NMDA receptors is increased during neonatal development. However, how the development of NMDA receptors influences EEG under volatile anesthesia remains unclear. Methods: Expressions of NMDA receptor subtypes (NR1, NR2A, and NR2B) during neonatal development were measured by Western blotting. MAC (minimal alveolar concentration) of isoflurane and sevoflurane that inducing loss of righting reflex (LORR) and no response to tail-clamp (immobility) were measured to verify the effect of NR1 expression on anesthetic potency during neonatal development. Cortical electroencephalogram recording was used to examine the influence of NR1 expression on the power density of EEG. Results: The expressions of GluNR1, GluNR2A and GluNR2B receptors were gradually increased during neonatal development in cortex, hippocampus and thalamus of rats. Knockdown of NR1 enhanced the sedative potency of volatile anesthetics but not on immobility potency in postnatal day 14 (P14)-P17 rats. For cortical EEG, along with the increased concentration of volatile anesthetics, cortical slow-delta oscillations of P5 rats were inhibited, theta and alpha oscillations were not changed significantly; while these oscillations were enhanced until high anesthetic concentrations in P21 rats. Knockdown of NR1 in forebrain suppressed the enhancement of cortical EEG oscillations in P21 rats. Conclusion: The development of NMDA receptors may contribute to the enhancement of cortical EEG oscillations under volatile anesthetics.
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Anestésicos por Inhalación , Corteza Cerebral , Electroencefalografía , Receptores de N-Metil-D-Aspartato , Animales , Ratas , Anestésicos por Inhalación/farmacología , Electroencefalografía/efectos de los fármacos , Isoflurano/farmacología , Receptores de N-Metil-D-Aspartato/metabolismo , Sevoflurano/farmacología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/embriologíaRESUMEN
Background: Liver transplantation (LT) is associated with a significant risk of intraoperative hemorrhage and massive blood transfusion. However, there are few relevant reports addressing the long-term impacts of massive transfusion (MT) on liver transplantation recipients. Aim: To assess the effects of MT on the short and long-term outcomes of adult liver transplantation recipients. Methods: We included adult patients who underwent liver transplantation at West China Hospital from January 2011 to February 2015. MT was defined as red blood cell (RBC) transfusion of ≥10 units within 48 hours since the application of LT. Preoperative, intraoperative and postoperative information were collected for data analyzing. We used one-to-one propensity-matching to create pairs. Kaplan-Meier survival analysis was used to compare long-term outcomes of LT recipients between the MT and non-MT groups. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors associated with MT in LT. Results: Finally, a total of 227 patients were included in our study. After propensity score matching, 59 patients were categorized into the MT and 59 patients in non-MT groups. Compared with the non-MT group, the MT group had a higher 30-day mortality (15.3% vs 0, p=0.006), and a higher incidence of postoperative complications, including postoperative pulmonary infection, abdominal hemorrhage, pleural effusion and severe acute kidney injury. Furthermore, MT group had prolonged postoperative ventilation support (42 vs 25 h, p=0.007) and prolonged durations of ICU (12.9 vs 9.5 d, p<0.001) stay. Multivariate COX regression indicated that massive transfusion (OR: 2.393, 95% CI: 1.164-4.923, p=0.018) and acute rejection (OR: 7.295, 95% CI: 2.108-25.246, p=0.02) were significant risk factors affecting long-term survivals of LT patients. The 1-year and 3-year survival rates patients in MT group were 82.5% and 67.3%, respectively, while those of non-MT group were 93.9% and 90.5%, respectively. The MT group exhibited a lower long-term survival rate than the non-MT group (HR: 2.393, 95% CI: 1.164-4.923, p<0.001). Finally, the multivariate logistic regression revealed that preoperative hemoglobin <118 g/L (OR: 5.062, 95% CI: 2.292-11.181, p<0.001) and intraoperative blood loss ≥1100 ml (OR: 3.212, 95% CI: 1.586-6.506, p = 0.001) were the independent risk factor of MT in patients undergoing LT. Conclusion: Patients receiving MT in perioperative periods of LT had worse short-term and long-term outcomes than the non-MT patients. Massive transfusion and acute rejection were significant risk factors affecting long-term survivals of LT patients, and intraoperative blood loss of over 1100 ml was the independent risk factor of MT in patients undergoing LT. The results may offer valuable information on perioperative management in LT recipients who experience high risk of MT.
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Pérdida de Sangre Quirúrgica , Transfusión Sanguínea/métodos , Trasplante de Hígado , Adulto , Pérdida de Sangre Quirúrgica/mortalidad , Transfusión Sanguínea/estadística & datos numéricos , Volumen Sanguíneo/fisiología , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Trasplante de Hígado/mortalidad , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Atención Perioperativa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Ethanol can induce acute stimulant responses in animals and human beings. Moreover, repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. The molecular mechanism of the development of acute stimulant responses and locomotor sensitization by ethanol is not fully understood. Sodium leak channel (NALCN) is widely expressed in central nervous system and controls the basal excitability of neurons. The present study aims to determine whether NALCN is implicated in the ethanol-induced acute responses and locomotor sensitization in mice. Here, our results showed that ethanol caused acute stimulant responses in DBA/2 mice. Locomotor sensitization was successfully induced following the sensitization procedure. Accordingly, the expression levels of NALCN mRNA and protein in the nucleus accumbens (NAc) were markedly increased in the sensitization mice compared to the control mice. Knockdown the expression levels of NALCN in the NAc alleviated both the ethanol-induced acute responses and locomotor sensitization. Our findings indicate that upregulation of NALCN expression in the NAc contributes to the ethanol-induced acute stimulant responses and locomotor sensitization in DBA/2 mice.
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BACKGROUND: Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. METHODS: The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. RESULTS: Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel-mediated holding currents and conductance from -75.0 ± 12.9 to -130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel-mediated holding conductance. CONCLUSIONS: Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.
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Anestésicos por Inhalación/administración & dosificación , Canales Iónicos/agonistas , Proteínas de la Membrana/agonistas , Neuronas/efectos de los fármacos , Respiración/efectos de los fármacos , Complejo Olivar Superior/efectos de los fármacos , Animales , Femenino , Canales Iónicos/fisiología , Masculino , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos C57BL , Neuronas/fisiología , Técnicas de Cultivo de Órganos , Canales de Sodio/fisiología , Complejo Olivar Superior/fisiologíaRESUMEN
General anesthetics are a class of drugs that target the central nervous system and are widely used for various medical procedures. General anesthetics produce many behavioral changes required for clinical intervention, including amnesia, hypnosis, analgesia, and immobility; while they may also induce side effects like respiration and cardiovascular depressions. Understanding the mechanism of general anesthesia is essential for the development of selective general anesthetics which can preserve wanted pharmacological actions and exclude the side effects and underlying neural toxicities. However, the exact mechanism of how general anesthetics work is still elusive. Various molecular targets have been identified as specific targets for general anesthetics. Among these molecular targets, ion channels are the most principal category, including ligand-gated ionotropic receptors like γ-aminobutyric acid, glutamate and acetylcholine receptors, voltage-gated ion channels like voltage-gated sodium channel, calcium channel and potassium channels, and some second massager coupled channels. For neural functions of the central nervous system, synaptic transmission is the main procedure for which information is transmitted between neurons through brain regions, and intact synaptic function is fundamentally important for almost all the nervous functions, including consciousness, memory, and cognition. Therefore, it is important to understand the effects of general anesthetics on synaptic transmission via modulations of specific ion channels and relevant molecular targets, which can lead to the development of safer general anesthetics with selective actions. The present review will summarize the effects of various general anesthetics on synaptic transmissions and plasticity.
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Anestésicos Generales/farmacología , Transmisión Sináptica/efectos de los fármacos , Animales , Canales de Calcio , Ácido Glutámico/efectos de los fármacos , Humanos , Isoflurano/farmacología , Estructura Molecular , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/efectos de los fármacos , Neurotransmisores , Sodio , Transmisión Sináptica/fisiología , Canales de Sodio Activados por Voltaje/efectos de los fármacos , Ácido gamma-Aminobutírico/efectos de los fármacosRESUMEN
Scalp nerve block with ropivacaine has been shown to provide perioperative analgesia. However, the best concentration of ropivacaine is still unknown for optimal analgesic effects. We performed a prospective study to evaluate the effects of scalp nerve block with varied concentration of ropivacaine on postoperative pain and intraoperative hemodynamic variables in patients undergoing craniotomy under general anesthesia. Eighty-five patients were randomly assigned to receive scalp block with either 0.2% ropivacaine, 0.33% ropivacaine, 0.5% ropivacaine, or normal saline. Intraoperative hemodynamics and post-operative pain scores at 2, 4, 6, 24 hours postoperatively were recorded. We found that scalp blockage with 0.2% and 0.33% ropivacaine provided adequate postoperative pain relief up to 2 h, while administration of 0.5% ropivacaine had a longer duration of action (up to 4 hour after craniotomy). Scalp nerve block with varied concentration of ropivacaine blunted the increase of mean arterial pressure in response to noxious stimuli during incision, drilling, and sawing skull bone. 0.2% and 0.5% ropivacaine decreased heart rate response to incision and drilling. We concluded that scalp block using 0.5% ropivacaine obtain preferable postoperative analgesia compared to lower concentrations. And scalp block with ropivacaine also reduced hemodynamic fluctuations in craniotomy operations.
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Anestésicos Locales/uso terapéutico , Craneotomía , Bloqueo Nervioso/métodos , Dolor Postoperatorio/tratamiento farmacológico , Ropivacaína/uso terapéutico , Cuero Cabelludo/inervación , Adulto , Anestesia Local/métodos , Anestésicos Locales/administración & dosificación , Craneotomía/métodos , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ropivacaína/administración & dosificaciónRESUMEN
BACKGROUND: Intraoperative blood salvage as a blood-saving strategy has been widely used in surgery. Considering its theoretic risk of malignant tumor cells being reinfused and the corresponding blood metastases, the safety of intraoperative blood salvage in cancer surgery remains controversial. METHODS: Following the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA), we searched the Cochrane Library, MEDLINE and EMBASE to November 2017. We included only studies comparing intraoperative blood salvage with allogeneic blood transfusion. RESULTS: This meta-analysis included 9 studies with 4354 patients with 1346 patients in the intraoperative blood salvage group and 3008 patients in the allogeneic blood transfusion group. There were no significant differences in the 5-year overall survival outcome (odds ratio [OR] 1.12; 95% confidence interval [CI], 0.80-1.58), 5-year disease-free survival outcome (OR 1.08; 95% CI 0.86-1.35), or 5-year recurrence rate (OR 0.86; 95% CI 0.71-1.05) between the 2 study groups. Subgroup analysis also showed no significant differences in the 5-year overall survival outcome (OR 0.97; 95% CI 0.57-1.67) of hepatocellular carcinoma patients in liver transplantation. CONCLUSIONS: For patients with malignant disease, intraoperative blood salvage did not increase the tumor recurrence rate and had comparable survival outcomes with allogeneic blood transfusion.
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Transfusión de Sangre Autóloga/efectos adversos , Recuperación de Sangre Operatoria/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/etiología , Neoplasias/cirugía , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
AIM: Acute kidney injury (AKI) commonly occurs in patients after liver transplantation (LT). However, few studies have focused on AKI and its correlation with clinical outcomes under the Kidney Disease Improving Global Outcomes (KDIGO) criteria. This study aimed to identity the incidence, risk factors, and impacts of early AKI on outcomes in LT recipients with normal preoperative renal function, according to the KDIGO criteria. METHODS: Clinical and laboratory data of 227 patients with normal preoperative renal function who underwent LT from January 2011 to January 2015 were retrospectively analyzed. RESULTS: During the first week after LT, 106 patients (46.7%) developed AKI based on the KDIGO criteria. A multivariate analysis revealed that BMI of > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, and post-operative RBC requirements > 10 units were independent risk factors for AKI after LT. The area under the receiver operating characteristic curve for the predictive ability of AKI under these risk factors was 0.748. The occurrence of AKI was associated with longer mechanical ventilation time and post-operative ICU stay, increased post-operative 30-day mortality and decreased long-term patient survival. CONCLUSIONS: Even in patients with normal preoperative renal function, AKI was a frequent complication in LT recipients and had both negative short- or long-term effects on patient outcomes, also the severity of AKI had a dose-response relationship with worse outcomes. Patients with BMI > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, or post-operative RBC requirement > 10 units should be pay particular attention, which may assist in achieving better clinical outcomes.
Asunto(s)
Lesión Renal Aguda/etiología , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/etiología , Lesión Renal Aguda/epidemiología , Adulto , Índice de Masa Corporal , Isquemia Fría/efectos adversos , Constricción , Transfusión de Eritrocitos , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC , Respiración Artificial/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Vena Cava Inferior , Isquemia TibiaRESUMEN
@#Objective To explore the effect of preoperative hypothyroidism on postoperative cognition dysfunction (POCD) in elderly patients after on-pump cardiac surgery. Methods Patients who were no younger than 50 years and scheduled to have on-pump cardiac surgeries were selected in West China Hospital from March 2016 to December 2017. Based on hormone levels, patients were divided into two groups: a hypo group (hypothyroidism group, thyroid stimulating hormone (TSH) >4.2 mU/L or free triiodothyronine 3 (FT3) <3.60 pmol/L or FT4 <12.0 pmol/L) and an eu group (euthyroidism group, normal TSH, FT3 and FT4). The mini-mental state examination (MMSE) test and a battery of neuropsychological tests were used by a fixed researcher to assess cognitive function on 1 day before operation and 7 days after operation. Primer outcome was the incidence of POCD. Secondary outcomes were the incidence of cognitive degradation, scores or time cost in every aspect of cognitive function. Results No matter cognitive function was assessed by MMSE or a battery of neuropsychological tests, the incidence of POCD in the hypo group was higher than that of the eu group. The statistical significance existed when using MMSE (55.56% vs. 26.67%, P=0.014) but was absent when using a battery of neuropsychological tests (55.56% vs. 44.44%, P=0.361). The incidence of cognitive deterioration in the hypo group was higher than that in the eu group in verbal fluency test (48.15% vs. 20.00%, P=0.012). The cognitive deterioration incidence between the hypo group and the eu group was not statistically different in the other aspects of cognitive function. There was no statistical difference about scores or time cost between the hypo group and the eu group in all the aspects of cognitive function before surgery. After surgery, the scores between the hypo group and the eu group was statistically different in verbal fluency test (26.26±6.55 vs. 30.23±8.00, P=0.023) while was not statistically significant in other aspects of cognitive function. Conclusion The incidence of POCD is high in the elderly patients complicated with hypothyroidism after on-pump cardiac surgery and words reserve, fluency, and classification of cognitive function are significantly impacted by hypothyroidism over than other domains, which indicates hypothyroidism may have close relationship with POCD in this kind of patients.