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OBJECTIVE: In this study, we evaluated the efficacy and safety of 1 µg/kg dexmedetomidine as an adjuvant treatment to ropivacaine in children undergoing upper limb surgeries under ultrasound-guided axillary brachial plexus blocks and general anesthesia. METHODS: We enrolled 90 children (aged 1-8 years; ASA I-II) undergoing closed reduction and internal fixation for upper extremity fractures at the Xiamen Children's Hospital and randomly assigned them to one of two groups: L (injection with 0.25% ropivacaine) or D (injection with 0.25% ropivacaine containing 1 µg/kg dexmedetomidine) using the random number table method. The main outcome indicators recorded were the facial expression, leg activity, position, crying, and Face, Legs, Activity, Cry, and Consolability (FLACC) scale scores of children after surgery and the duration of block and analgesia maintenance. The secondary outcome indicators were vital sign data at the time of ultrasound probe placement (T1), at the time of block completion (T2), prior to the beginning of surgery (T3), 5 min after the beginning of surgery (T4), and at the end of surgery (T5), as well as the time of postoperative recovery, the number of cases of remedial analgesia, and complications. RESULTS: There was no statistical difference between the two groups in terms of general data, block completion time, postoperative recovery time, and complications (P > 0.05). Compared to the L group, the D group had significantly lower FLACC scores at 6 h after surgery, as well as significantly lower systolic blood pressure, diastolic blood pressure, and heart rate values at T4 and T5, and significantly longer duration of postoperative analgesia maintenance (all P < 0.05). CONCLUSION: Dexmedetomidine (1 µg/kg) as a local anesthetic adjuvant to ropivacaine can alleviate pain at 6 h postoperatively, prolong analgesia maintenance, and reduce intraoperative blood pressure and heart rate in pediatric patients undergoing closed reduction and internal fixation for upper extremity fractures, with no obvious complications or delayed recovery. CLINICAL REGISTRY NUMBER: Registration website: www.chictr.org.cn, Registration number: ChiCTR2200065163, Registration date: October, 30, 2022.
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Bloqueo del Plexo Braquial , Dexmedetomidina , Ropivacaína , Humanos , Dexmedetomidina/administración & dosificación , Ropivacaína/administración & dosificación , Bloqueo del Plexo Braquial/métodos , Masculino , Femenino , Preescolar , Niño , Lactante , Anestésicos Locales/administración & dosificación , Ultrasonografía Intervencional/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Plexo Braquial/diagnóstico por imagen , Plexo Braquial/efectos de los fármacosRESUMEN
PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.
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Citocinas , Ketamina , Pulmón , FN-kappa B , Estrés Oxidativo , Enfermedad Pulmonar Obstructiva Crónica , Ratas Sprague-Dawley , Transducción de Señal , Animales , Ketamina/uso terapéutico , Ketamina/farmacología , Estrés Oxidativo/efectos de los fármacos , FN-kappa B/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Masculino , Citocinas/metabolismo , Ratas , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/inmunología , Transducción de Señal/efectos de los fármacos , Lesión Pulmonar Inducida por Ventilación Mecánica/tratamiento farmacológico , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de Enfermedad , Respiración Artificial/efectos adversos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismoRESUMEN
Eleven undescribed monoterpenoid bisindole alkaloids, alstomaphyines A-K (1-11), along with three known analogues were isolated from the leaves and stem bark of the Alstonia macrophylla. Compounds 1-3 were unprecedented dimerization alkaloids incorporating a macroline-type motif with an ajmaline-type motif via a C-C linkage. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and CD exciton chirality method. Compounds 1-3 displayed potential inhibitory bioactivity against AChE with IC50 values of 4.44 ± 0.35, 3.59 ± 0.18, and 3.71 ± 0.23 µM, respectively. Enzyme kinetic study revealed compounds 1-3 as mixed competitive AChE inhibitors. Besides, compounds 8 and 12-14 exhibited better cytotoxicity against human cancer cell line HT-29 than cisplatin. Flow cytometry data revealed that compounds 8, 13, and 14 significantly induced the HT-29 cells arrest in G0/G1 phase in a concentration-dependent manner.
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Four new alkaloids, arecatines A-D (1-4), were isolated from the peels of Areca catechu. Compound 1 is an unusual piperidine-pyridine hybrid alkaloid, whereas compounds 2-4 feature bis-piperidine alkaloids. Their structures were elucidated by UV, IR, HRESIMS, and NMR spectra analysis. The molecular docking analysis indicated that compound 3 exhibited the best binding affinity with the GABAA receptor, indicating its potential anti-epilepsy activity.
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AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.
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Glucemia , Enfermedades Cardiovasculares , Ayuno , Carga Global de Enfermedades , Humanos , Masculino , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Femenino , Persona de Mediana Edad , Glucemia/análisis , Adulto , Anciano , Ayuno/sangre , Estudios de Seguimiento , Pronóstico , Factores de Riesgo , Adulto Joven , Costo de EnfermedadRESUMEN
Tripterygium wilfordii has been historically employed as a conventional botanical insecticide and a plant of medicinal significance. A new dihydroagarofuran sesquiterpene (1) and a new acyclic compound (2), along with seven known compounds (3-9), have been isolated from the aerial parts of Tripterygium wilfordii. The identification of the structures of novel compounds were accomplished through comprehensive spectroscopic analyses, encompassing HRESIMS, NMR, UV, IR, and a comparative analysis with spectroscopic data from compounds previously characterised. In in-vitro bioassay, compound 8 exhibited significant inhibitory activity for NO release in LPS-induced RAW 264.7 cells, with an IC50 value of 15.7 µM.
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Parkinson's disease (PD) is a ubiquitous brain cell degeneration disease and presents a significant therapeutic challenge. By injecting 6-hydroxydopamine (6-OHDA) into the left medial forebrain bundle, rats were made to exhibit PD-like symptoms and treated by intranasal administration of a low-dose (2 × 105) or high-dose (1 × 106) human neural stem cells (hNSCs). Apomorphine-induced rotation test, stepping test, and open field test were implemented to evaluate the motor behavior and high-performance liquid chromatography was carried out to detect dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindole-3-acetic acid in the striatum of rats. Animals injected with 6-OHDA showed significant motor function deficits and damaged dopaminergic system compared to the control group, which can be restored by hNSCs treatment. Treatment with hNSCs significantly increased the tyrosine hydroxylase-immunoreactive cell count in the substantia nigra of PD animals. Moreover, the levels of neurotransmitters exhibited a significant decline in the striatum tissue of animals injected with 6-OHDA when compared to that of the control group. However, transplantation of hNSCs significantly elevated the concentration of DA and DOPAC in the injured side of the striatum. Our study offered experimental evidence to support prospects of hNSCs for clinical application as a cell-based therapy for PD.
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INTRODUCTION: We analyzed the effect of dexmedetomidine (DEX) as a local anesthetic adjuvant on postoperative delirium (POD) in elderly patients undergoing elective hip surgery. METHODS: In this study, 120 patients undergoing hip surgery were enrolled and randomly assigned to two groups: fascia iliaca compartment block with DEX + ropivacaine (the Y group, n = 60) and fascia iliaca compartment block with ropivacaine (the R group, n = 60). The primary outcomes: presence of delirium during the postanesthesia care unit (PACU) period and on the first day (D1), the second day (D2), and the third day (D3) after surgery. The secondary outcomes: preoperative and postoperative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), occurrence of insomnia on the preoperative day, day of operation, D1 and D2; HR values of patients in both groups before iliac fascia block (T1), 30 min after iliac fascia block (T2), at surgical incision (T3), 20 min after incision (T4), when they were transferred out of the operating room (T5) and after leaving the recovery room (T6) at each time point; VAS for T1, PACU, D1, D2; the number of patients requiring remedial analgesics within 24 h after blockade and related complications between the two groups. RESULTS: A total of 97 patients were included in the final analysis, with 11 and 12 patients withdrawing from the R and Y groups, respectively. The overall incidence of POD and its incidence in the PACU and ward were all lesser in the Y group than in the R group (p < 0.05). Additionally, fewer cases required remedial analgesia during the PACU period, and more vasoactive drugs were used for maintaining circulatory system stability in the Y group as compared to the R group (p < 0.05). At the same time, the incidence of intraoperative and postoperative bradycardia in the Y group was higher than that in the R group, accompanied by lower postoperative CRP and ESR (all p < 0.05). CONCLUSION: Ultrasound-guided high fascia iliaca compartment block with a combination of ropivacaine and DEX can reduce the incidence of POD, the use of intraoperative opioids and postoperative remedial analgesics, and postoperative inflammation in elderly patients who have undergone hip surgery, indicating that this method could be beneficial in the prevention and treatment of POD.
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Anestésicos Locales , Dexmedetomidina , Procedimientos Quirúrgicos Electivos , Bloqueo Nervioso , Ropivacaína , Humanos , Dexmedetomidina/administración & dosificación , Masculino , Anciano , Femenino , Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Ropivacaína/administración & dosificación , Procedimientos Quirúrgicos Electivos/efectos adversos , Procedimientos Quirúrgicos Electivos/métodos , Fascia , Anciano de 80 o más Años , Delirio del Despertar/prevención & control , Delirio del Despertar/epidemiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Cadera/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodosRESUMEN
One undescribed homologous furanochromanone (1) featuring a 6/6/5/3 tetracyclic skeleton and four highly oxidized pyranochromanones (2-5), along with a set of four pyranochromanone stereoisomers [(±)-6a and (±)-6b], were isolated from the leaves of Calophyllum membranaceum Gardn. Et Champ. Their structures were elucidated by using spectroscopic data, Snatzke's method, quantum-chemical calculations, and X-ray crystallographic analysis. The correlation of characteristic Cotton effects and specific chemical shifts with C-3 configuration provided a convenient approach to assign the C-3 configuration of 2,3-dimethylchromanones. The stereochemical assignments of 3-OH substituted pyranochromanones by quantum-based NMR methods following single/double MTPA derivatization were consistent with the ECD/NMR prediction, which verified the feasibility and reliability of the proposed empirical rule. The underlying mechanism was further clarified by conformational and molecular orbital analyses. Moreover, biological evaluation and binding assays demonstrated that compound 3 (KD = 0.45 µM) tightly binds to the TLR4-MD2 target, thereby inhibiting the TLR4/MyD88-dependent and -independent signal pathways. This study provides the first evidence that Calophyllum chromanones are a novel structural type of TLR4 inhibitors, exerting their anti-inflammatory effects by disrupting the binding between TLR4 and MD2.