RESUMO
Psychological stress induces neuroinflammatory responses, which are associated with the pathogenesis of various psychiatric disorders, such as posttraumatic stress disorder and anxiety. Osthole-a natural coumarin isolated from the seeds of the Chinese herb Cnidium monnieri-exerts anti-inflammatory and antioxidative effects on the central nervous system. However, the therapeutic benefits of osthole against psychiatric disorders remain largely unknown. We previously demonstrated that mice subjected to repeated social defeat stress (RSDS) in the presence of aggressor mice exhibited symptoms of posttraumatic stress disorder, such as social avoidance and anxiety-like behaviors. In this study, we investigated the therapeutic effects of osthole and the underlying molecular mechanisms. Osthole exerted therapeutic effects on cognitive behaviors, mitigating anxiety-like behaviors and social avoidance in a mouse model of RSDS. The anti-inflammatory response induced by the oral administration of osthole was strengthened through the upregulation of heme oxygenase-1 expression. The expression of PPARα was inhibited in mice subjected to RSDS. Nonetheless, osthole treatment reversed the inhibition of PPARα expression. We identified a positive correlation between heme oxygenase-1 expression and PPARα expression in osthole-treated mice. In conclusion, osthole has potential as a Chinese herbal medicine for anxiety disorders. When designing novel drugs for psychiatric disorders, researchers should consider targeting the activation of PPARα.
RESUMO
Macrophages and microglia are highly versatile cells that can be polarized into M1 and M2 phenotypes in response to diverse environmental stimuli, thus exhibiting different biological functions. In the central nervous system, activated resident macrophages and microglial cells trigger the production of proinflammatory mediators that contribute to neurodegenerative diseases and psychiatric disorders. Therefore, modulating the activation of macrophages and microglia by optimizing the inflammatory environment is beneficial for disease management. Several naturally occurring compounds have been reported to have anti-inflammatory and neuroprotective properties. Zerumbone is a phytochemical sesquiterpenoid and also a cyclic ketone isolated from Zingiber zerumbet Smith. In this study, we found that zerumbone effectively reduced the expression of lipocalin-2 in macrophages and microglial cell lines. Lipocalin-2, also known as neutrophil gelatinase-associated lipocalin (NGAL), has been characterized as an adipokine/cytokine implicated in inflammation. Moreover, supplement with zerumbone inhibited reactive oxygen species production. Phagocytic activity was decreased following the zerumbone supplement. In addition, the zerumbone supplement remarkably reduced the production of M1-polarization-associated chemokines CXC10 and CCL-2, as well as M1-polarization-associated cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α. Furthermore, the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 and the production of NO were attenuated in macrophages and microglial cells supplemented with zerumbone. Notably, we discovered that zerumbone effectively promoted the production of the endogenous antioxidants heme oxygenase-1, glutamate-cysteine ligase modifier subunit, glutamate-cysteine ligase catalytic subunit, and NAD(P)H quinone oxidoreductase-1 and remarkably enhanced IL-10, a marker of M2 macrophage polarization. Endogenous antioxidant production and M2 macrophage polarization were increased through activation of the AMPK/Akt and Akt/GSK3 signaling pathways. In summary, this study demonstrated the protective role of zerumbone in maintaining M1 and M2 polarization homeostasis by decreasing inflammatory responses and enhancing the production of endogenous antioxidants in both macrophages and microglia cells. This study suggests that zerumbone can be used as a potential therapeutic drug for the supplement of neuroinflammatory diseases.
Assuntos
Glutamato-Cisteína Ligase , Sesquiterpenos , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/farmacologia , Lipocalina-2 , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Citocinas/metabolismo , Microglia , Macrófagos/metabolismo , Sesquiterpenos/farmacologia , Sesquiterpenos/metabolismo , Interleucina-6/metabolismo , OxirreduçãoRESUMO
BACKGROUND: Many tools have been developed to facilitate the insertion of the ProSeal laryngeal mask airway (LMA) insertion, which can be impeded by folding of its soft cuff. The aim of this study was to compare the efficiency of ProSeal LMA insertion guided by a soft, direct optical Foley Airway Stylet Tool (FAST) with the standard introducer tool (IT). METHODS: One hundred sixty patients undergoing general anesthesia using the ProSeal LMA as an airway management device were randomly allocated to either FAST-guided or IT-assisted groups. Following ProSeal LMA insertion, the glottic and esophageal openings were identified using a fiberoptic bronchoscope introduced through the airway and the drain tube. The primary outcomes were time taken to insert the ProSeal LMA and the success rate at the first attempt. Secondary end points included ease of insertion, hemodynamic response to insertion, and postoperative adverse events recorded in the recovery room and on the first postoperative morning. RESULTS: One hundred forty patients were included in the final analysis: 66 in the FAST-guided group and 74 in the IT-assisted group. The success rate of FAST device-guided ProSeal LMA insertion (95.7%) was broadly comparable with IT-assisted insertion (98.7%). However, the time taken to insert the ProSeal LMA was significantly longer when the FAST technique was used (p <0.001). The incidence of correct alignment of the airway tube and the drain tube did not differ significantly between the groups. There were no significant differences in ease of insertion or hemodynamic responses to insertion, except that the incidence of postoperative sore throat was significantly higher in the FAST group on the first postoperative day (22.2% compared with 6.8% in the IT group; p = 0.035). CONCLUSION: Both FAST-guided and IT-assisted techniques achieved correct ProSeal LMA positioning, but the IT technique was significantly quicker and less likely to cause a sore throat. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02048657.
Assuntos
Manuseio das Vias Aéreas/métodos , Anestesia Geral/métodos , Máscaras Laríngeas , Adulto , Idoso , Manuseio das Vias Aéreas/instrumentação , Broncoscópios , Broncoscopia/métodos , Desenho de Equipamento , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , Pessoa de Meia-Idade , Faringite/epidemiologia , Estudos Prospectivos , Fatores de Tempo , Adulto JovemRESUMO
The enlarged adenoid serves as a mechanical obstacle on the nasopharynx to intricate nasotracheal intubation. No matter what video or direct laryngoscopic techniques are applied, nasotracheal tube navigation from the nasal valve area through the nasal cavity to the nasopharynx is always blind; trauma is not uncommon. Here we report a case of unintended avulsed adenoids that plugged the tube tip while the nasotracheal tube blindly navigated through the nasopharyngeal space. After failing to insert a bent tip of gum elastic bougie passing through the nasopharynx, an alternative method of NTI was performed by mounting the nasotracheal tube on a fiberoptic bronchoscope. The nasotracheal tube was successfully railroaded along the insertion tube of the fiberscope to the trachea.
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Epidural morphine in patient-controlled analgesia regimens controls postoperative pain well but easily induces pruritus and other epidural morphine-related side effects. With 90 pregnant American Society of Anesthesiologists physical status II females scheduled for elective cesarean delivery, the present study was designed to evaluate the efficacy and safety profile of patient-controlled antipruritus (PCP) use of intravenous nalbuphine-based regimens for attenuation of postoperative pruritus and related side effects in combination with epidural morphine patient-controlled analgesia with regard to the quality of postoperative pain management. Patients were randomly assigned to two nalbuphine groups (5 µg/kg/hour, Group N5 or 10 µg/kg/hour, Group N10) and bolus dose of 1.6 µg/kg for PCP or the control (normal saline) group. Comparable visual analog scale scores for rest pain at each measured time interval among the three groups demonstrated that adequate pain relief was offered; however, the cumulative dose of nalbuphine administered to the patients in Group N10 attenuated the analgesic effect of epidural morphine in moving pain at POh24 only. Fewer episodes and milder severity of pruritus were observed in patients in Groups N5 and N10 at all postoperative time intervals. Epidural morphine provided good postoperative pain relief but with incommodious side effects. In addition, intravenous nalbuphine not only attenuated the incidence of pruritus but also decreased total morphine consumption. In conclusion, intravenous administration of low-dose nalbuphine (5 µg/kg/hour) for PCP maintained analgesia produced by epidural morphine and offered low pruritus incidence.
Assuntos
Analgesia Epidural , Cesárea , Morfina/efeitos adversos , Nalbufina/farmacologia , Prurido/induzido quimicamente , Adulto , Analgesia Controlada pelo Paciente , Cesárea/efeitos adversos , Demografia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Morfina/administração & dosagem , Morfina/farmacologia , Nalbufina/administração & dosagem , Medição da Dor , Dor Pós-Operatória/etiologia , Gravidez , Adulto JovemRESUMO
A young female patient scheduled for orthognathic surgery under general anesthesia encountered obstacles during nasotracheal intubation in which the cuff of the nasal endotracheal tube was linearly lacerated and the tube tip impacted against the retropharyngeal wall. Repeated episodes of the event happened rendering the intubation unsuccessful. A technique using modified glove fingers was applied, which successfully protected the cuff from shearing by the sharp nasal crista and redirected the tube tip away from the retropharyngeal wall. It is a simple and applicable technique during nasotracheal intubation to prevent cuff damage and potential retropharyngeal dissection.
Assuntos
Intubação Intratraqueal/métodos , Adulto , Feminino , Humanos , Cavidade Nasal , Adulto JovemRESUMO
OBJECTIVES: To determine if the intravenous co-administration of equal volumes of lidocaine and nalbuphine, with undiluted normal saline, prevents injection pain caused by nalbuphine. METHODS: Eighty adult patients who were scheduled for minor surgeries under general anesthesia delivered via a laryngeal mask airway (LMA) were enrolled in this prospective, randomized, single-blind clinical trial. In the saline group (control) (n = 40), 1 mL (10 mg) nalbuphine was diluted with 9 mL normal saline. In the lidocaine group (experimental) (n = 40), 1 mL (10 mg) nalbuphine was diluted with 1 mL lidocaine (20 mg). The two respective nalbuphine solutions were injected into the cephalic vein at a rate of 20 mL/minute (0.33 mL/second). Pain scores were categorized into five grades. Pain responses upon intravenous injection of nalbuphine, site of cannulation, size of the catheter, and hemodynamic responses to nalbuphine were also recorded. RESULTS: Overall, the median pain score of patients in the lidocaine group was lower than that of the saline group (p < 0.001). In addition, the incidence of injection pain was lower in the lidocaine group than the saline group (2.5% vs. 30%, p = 0.001). CONCLUSION: A solution of equal volumes of lidocaine and nalbuphine can decrease intravenous nalbuphine-induced injection pain.