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1.
Artigo em Inglês | MEDLINE | ID: mdl-39032105

RESUMO

AIM: Surgery for congenital scoliosis correction in children is often associated with considerable blood loss. Decrease in regional oxygen saturation (rScO2) can reflect insufficient cerebral perfusion and predict neurological complications. This retrospective observational study explored the relationship between blood loss during this surgery and a decrease in rScO2 in children. METHODS: The following clinical data of children aged 3-14 years who underwent elective posterior scoliosis correction between March 2019 and July 2021 were collected: age, sex, height, weight, baseline rScO2, basal mean invasive arterial pressure (MAP), preoperative Cobb angle, number of surgical segments, preoperative and postoperative haemoglobin level, percentage of lowest rScO2 below the baseline value that lasted 3 min or more during the operation (decline of rScO2 from baseline, D-rScO2%), intraoperative average invasive MAP, end-tidal carbon dioxide pressure, fluid infusion rate of crystalloids and colloids, operation time, and percentage of total blood loss/patient's blood volume (TBL/PBV). RESULTS: A total of 105 children were included in the study. Massive haemorrhage (TBL/PBV ≥50%) was reported in 53.3% of patients, who had significantly higher D-rScO2 (%) (t = -5.264, P < 0.001) than those who had non-massive haemorrhage (TBL/PBV <50%). Multiple regression analysis revealed that TBL/PBV (ß = 0.04, 95% CI: 0.018-0.062, P < 0.05) was significantly associated with D-rScO2%. CONCLUSIONS: Intraoperative massive blood loss in children significantly increased D-rScO2%. Monitoring should be improved, and timely blood supplementation should be performed to ensure maintenance of the blood and oxygen supply to vital organs, improve the safety of anaesthesia, and avoid neurological complications.

2.
Clin Pediatr (Phila) ; 63(2): 249-256, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37042054

RESUMO

This study described electroencephalogram (EEG) parameters in children under general anesthesia, which could monitor patient-specific brain responses to anesthetics and assess the effects of anesthesia. The objective was to detect the patient state index (PSI) and associated factors. We analyzed EEG parameters in patients in the age range 1 to 36 months. Patients were stratified into 2 groups as those aged 1 to 12 months and 13 to 36 months. Sixty-two patients were involved. Spectral edge frequency (SEF), PSI, and blood pressure were lower, and burst suppression rate (BSR) and heart rate were higher in the 1 to 12 months group. The SEF was associated with PSI in both groups. Age and blood pressure were positively associated with PSI, and BSR was negatively related to PSI in children under 1 year of age. Blood pressure was not associated with PSI in the 13 to 36 months age group. We found that the PSI levels did not accurately assess the depth of anesthesia in children under 1 year of age.


Assuntos
Anestesia Geral , Anestésicos , Lactente , Criança , Humanos , Pré-Escolar , Estudos Retrospectivos , Eletroencefalografia , Pressão Sanguínea
3.
Hepatol Commun ; 7(11)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37851406

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction-associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.


Assuntos
Fígado Gorduroso , Síndrome Metabólica , Humanos , Algoritmos , Perfilação da Expressão Gênica , Receptores de Quimiocinas
4.
BMC Anesthesiol ; 23(1): 261, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542220

RESUMO

BACKGROUND: It is believed that negative postoperative behavioral changes (NPOBC) is associated with negative perioperative outcomes in children. The importance of development of a predictive model of NPOBC was noted. This study aims to identify potential risk factors develop a nomogram to predict NPOBC on postoperative day 3 based on a prospective cohort. METHODS: A prospective observational study was conducted on children(American Society of Anesthesiologists I ~ III) aged 2 ~ 12 years who underwent selective surgery under general anesthesia between September 2022 and February 2023. The patient's clinical data were analyzed. The method of measuring NPOBC is with the The Posthospital Behaviour Questionnaire (PHBQ), and all of children remained hospitalized at the time of assessment. The enrolled patients were categorized into the NPOBC group and the non-NPOBC group according to if children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop the nomogram to predict NPOBC. Internal validation was performed using the parametric bootstrapping method. RESULTS: One hundred ninety-two patients were enrolled in the study, 44.8% (86/192 patients) of children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analysis demonstrated that the Pediatric Anesthesia Behavior (PAB) score (OR: 1.23, 95%CI: 1.14-1.33), cerebral desaturation (OR: 1.16, 95%CI: 1.02-1.32), and postoperative pain score (OR: 1.07, 95%CI: 1.02-1.13) were independent predictors for NPOBC on postoperative day 3 (P < 0.05). They were used to develop the prediction model. The calibration curve demonstrated satisfied discrimination and calibration of the prediction model. The model presented with good discriminative ability (area under the receiver operating characteristic curve: 0.762 [95%CI: 0.691-0.833]). The decision curve analysis also revealed the great clinical utility of the nomogram. CONCLUSION: Based on our prospective observational study, pre-anesthesia patients with higher PAB scores, presence of cerebral desaturation, and higher postoperative pain score were more likely to develop NPOBC on postoperative day 3. We established and validated a nomogram for predicting NPOBC, which could help assess patients individually, identify high-risk groups of NPOBC and improve patient prognosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,200,059,776. Registered 11 May 2022.


Assuntos
Anestesia Geral , Nomogramas , Criança , Humanos , Anestesia Geral/efeitos adversos , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos
5.
Trials ; 24(1): 481, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37501064

RESUMO

BACKGROUND: Emergence delirium (ED) in children refers to the immediate postoperative period when children experience decreased perception of their surroundings, accompanied by disorientation and altered perception. Burst suppression (BS) is recognised as periods longer than 0.50 s during which the EEG does not exceed approximately + 5.0 mV, which is an electroencephalographic state associated with profound inactivation of the brain. Our primary objective was to determine the association between BS on electroencephalogram (EEG) under general anaesthesia with postoperative wake-up delirium and multiple adverse outcomes, such as prolonged awakening and extubation. METHODS: In this prospective, observational cohort study at Beijing Children's Hospital, Capital Medical University, Beijing, China, children aged 6 months to 9 years who underwent surgery under general anaesthesia and underwent EEG monitoring between January 2022 and January 2023 were included. Patients' prefrontal EEGs were recorded intraoperatively as well as analysed for the occurrence and duration of BS and scored postoperatively for delirium by the PAED scale, with a score of no less than 10 considered as having developed wake-up delirium. DISCUSSION: This study identified a relationship between EEG BS and postoperative awakening delirium under general anaesthesia in children and provides a novel preventive strategy for postoperative awakening delirium and multiple adverse outcomes in paediatric patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200055256. Registered on January 5, 2022.


Assuntos
Delírio do Despertar , Humanos , Criança , Estudos Prospectivos , Delírio do Despertar/etiologia , Eletroencefalografia , Anestesia Geral/efeitos adversos , Anestesia Geral/métodos , Período de Recuperação da Anestesia , Prognóstico , Estudos Observacionais como Assunto
6.
Front Pediatr ; 11: 1117455, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37360360

RESUMO

Objectives: To assess whether decreased regional cerebral oxygen saturation (rScO2) is associated with the emergence delirium (ED) following general anesthesia in the pediatric population. Methods: A retrospective observational cohort study was conducted on 113 children (ASA I-III) aged 2-14 years who underwent selective surgery under general anesthesia between 2022-01 and 2022-04. Intraoperatively, the rScO2 was monitored using a cerebral oximeter. The Pediatric Anesthesia Emergence Delirium (PAED) score was used to evaluate the patients for ED. Results: The incidence of ED was 31%. Low rScO2 was reported in 41.6% of patients, who had a higher incidence of ED (P < 0.001) than those who did not experience desaturation. Logistic regression analysis revealed that decreased rScO2 was significantly associated with incident ED events [odds ratio (OR), 10.77; 95% confidence interval, 3.31-35.05]. Children under 3 years of age had a higher incidence of ED after rScO2 desaturation during anesthesia compared to older children (OR, 14.17 vs. 4.64). Conclusion: Intraoperative rScO2 desaturation significantly increased the incidence of ED following general anesthesia. Monitoring should be enhanced to improve the oxygen balance in vital organs to improve the quality and safety of anesthesia.

7.
Front Pediatr ; 10: 956660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052360

RESUMO

Purpose: Tonsillectomy is a recognized treatment for children with tonsil hypertrophy and results in significant postoperative oropharyngeal pain. Fentanyl and other morphine-like analgesics are widely used as perioperative analgesia but are associated with side effects such as vomiting, nausea, and respiratory depression. As the least toxic non-steroidal anti-inflammatory drug, ibuprofen may be effective and safe for pain control after tonsillectomy. We aimed to explore whether the addition of intravenous (IV) ibuprofen administered at induction can reduce the need for early postoperativeanalgesics. Study design and methods: This randomized, double-blind, controlled clinical trial enrolled 95 pediatric patients who underwent tonsillectomy. Participants aged 6 months to 12 years were randomly assigned to either the experimental and control groups (1:1). The children were premedicated 15 min before surgery with IV ibuprofen 10 mg kg-1 or placebo (normal saline). Pain was scored at 15, 30, and 120 min after extubation, and IV fentanyl (0.5 mcg kg-1) was administered when the Faces, Legs, Activity, Cry, and Consolability (FLACC) Scale was ≥7 and deemed appropriate by the nursing staff in the post-anesthesia care unit (PACU). The visual analog scale was used as a supplementary evaluation for older children (≥7 years old) who were awake and could self-report pain. The primary outcome variable was the number of patients who received postoperative analgesia. Results: The requirement for rescue fentanyl was reduced by 18% with the addition of IV ibuprofen (P = 0.043). There were no signficant differences in the amount of fentanyl administered postoperatively (P = 0.127). Compared with the placebo group, the number of children who needed more than one dose of rescue fentanyl decreased in the experimental group, but the differences were not significant (P = 0.056). There were no significant differences between the groups in terms of operative blood loss (P = 0.978), vomiting, or postoperative bleeding (P = 0.474). Conclusion: It is safe to administer IV ibuprofen 15 min before tonsillectomy, and it can significantly reduce the need for rescue fentanyl. IV ibuprofen should be considered as an important part of the multimodal approach for postoperative analgesia in children. Clinical trial registration: Chictr.org.cn, identifier: ChiCTR2100044508.

8.
J Pain Res ; 15: 1401-1410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592817

RESUMO

Background: Emergence agitation (EA) has a negative effect on the recovery from general anesthesia in children. This study aimed to evaluate the effectiveness of intravenous ibuprofen in reducing the incidence of EA in children. Methods: This randomized, double-blind, placebo-controlled, single-center study analyzed data from patients aged 3-9 years undergoing tonsillectomy under general anesthesia with propofol and remifentanil. These patients were randomly assigned to receive either the ibuprofen or the placebo intraoperatively. The primary endpoint was a between-group difference in the incidence of EA at 15 min following extubation. EA was defined as Pediatric Anesthesia Emergence Delirium score ≥10. The secondary endpoint included the associated factors of EA. Results: Eighty-nine patients were included in the study. Ibuprofen decreased the incidence of EA at 15 min following extubation (8.9% in the treatment group vs 34.1% in the control group; odds ratio [OR], 0.261; 95% confidence interval [CI], 0.094-0.724; P=0.004). Compared with the control group, there was a significant reduction in the number of rescue fentanyl doses (P=0.045), and fewer patients experienced moderate to severe pain at 15 min following extubation in the treatment group (P=0.048). Upon logistic regression analysis, high modified Pediatric Anesthesia Behavior and pain scores following surgery were considered the risk factors related to EA (OR, 8.07; 95% CI, 1.12-58.07, P=0.038 and OR, 2.78; 95% CI, 1.60-4.82, P<0.001, respectively). Ibuprofen administration was the protective factor related to EA (OR, 0.05; 95% CI, 0.01-0.67, P=0.023). Conclusion: Intraoperative ibuprofen infusion can significantly reduce the incidence of EA following general anesthesia with propofol and remifentanil in children. Trial Registration: The study was registered with the Chinese Clinical Trial Registry on 7 April 2021 (number: ChiCTR2100045128; https://www.chictr.org.cn/edit.aspx?pid=124595&htm=4).

9.
Comput Math Methods Med ; 2022: 7606716, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35469222

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become one of the problems affecting the health of the population worldwide. The progressive disease includes nonalcoholic steatohepatitis (NASH) and fibrosis, which with no approved therapy, system identification of effective drugs remains challenging. In this work, we applicated drug perturbation gene set enrichment analysis to screen drugs for the development of NAFLD. A total 15490 small-molecule compounds were analyzed in our study; based on the p value of enrichment score, 7 small-molecule compounds were found to have a potential role in NASH and fibrosis. After pathway analyses, we found indoximod had effects on nonalcoholic fatty liver disease through regulated TNFa, AP-1, AKT, PI3K, etc. Furthermore, we established the NAFLD cell model with LO2 cells induced using PA; ELISA showed that the levels of TG, ALT, and AST were significantly improved by indoximod. In summary, our study offers optimal therapeutic drugs, which may provide novel insight into the precise treatment of NAFLD and promote researches.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Fibrose , Humanos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética
11.
Front Pediatr ; 10: 1051069, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36683807

RESUMO

Background: Thoracoscopy is considered the surgical method of choice for addressing a wide range of conditions in neonates. However, there is a lack of experience in anesthesia management for this procedure. On reviewing the newborns who had undergone thoracoscopic surgery at our medical center, some had developed edema after surgery. After excluding other etiologies, these neonates were diagnosed with capillary leakage secondary to thoracoscopy. Aims: This study aimed to identify the potential risk factors for capillary leakage secondary to thoracoscopy in neonates and to provide reference information for optimal anesthesia management. Methods: This single-center, retrospective, observational study examined neonates who had undergone thoracoscopic surgery between January 1, 2018, and September 31, 2021. Their electronic medical records were analyzed for demographic and clinical characteristics associated with anesthesia, and postoperative capillary leakage occurring within 24 and 48 h of surgery was assessed based on medical records. Results: A total of 56 neonates that underwent thoracoscopic surgery were included in this study. Postoperative capillary leakage within 24 h was diagnosed in 14 neonates (25%). The partial pressure of carbon dioxide was an independent factor influencing the occurrence of postoperative edema within 24 h (P = 0.021). Overall, 21 cases (37.5%) were diagnosed as postoperative capillary leakage within 48 h, and age was an independent factor influencing the occurrence of postoperative edema within 48 h (P = 0.027). Conclusions: According to our findings, we concluded that preventing the elevation of the partial pressure of carbon dioxide may reduce the occurrence of secondary capillary leakage within 24 h after thoracoscopic surgery, and that older newborns are less likely to have secondary capillary leakage within 48 h after thoracoscopic surgery. Our findings provide evidence that directly informs anesthesia management for thoracoscopic surgery in neonates. Clinical trial registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100054117).

12.
Pediatr Investig ; 5(4): 271-276, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34938968

RESUMO

IMPORTANCE: In children, anesthesia dosages are based on population pharmacokinetics and patient hemodynamics rather than patient-specific brain activity. Brain function is highly susceptible to the effects of anesthetics. OBJECTIVE: The primary objective of this retrospective pilot study was to assess the prevalence of electroencephalography (EEG) burst suppression-a sign of deep anesthesia-in children undergoing general anesthesia. METHODS: We analyzed EEG in patients aged 1-36 months who received sevoflurane or propofol as the primary anesthetic. Patient enrollment was stratified into two age groups: 1-12 months and 13-36 months. Burst suppression (voltage ≤ 5.0 mV, lasting > 0.5 seconds) was characterized by occurrence over anesthesia time. Associations with patient demographics and anesthetics were determined. RESULTS: In total, 54 patients (33 males and 21 females) were included in the study [age 11.0 (5.0-19.5) months; weight 9.2 (6.5-11.0) kg]. The total prevalence of burst suppression was 56% (30/54). Thirty-three percent of patients experienced burst suppression during the surgical phase. The greatest proportion of burst suppression occurred during the induction phase. More burst suppression event occurrences (18/30) were observed in the patient under sevoflurane anesthesia (P = 0.024). Virtually all patients who received propofol boluses had burst suppression (P = 0.033). More burst suppression occurred in patients with hypotension (P < 0.001). During the surgical phase, a younger age was associated with more burst suppression (P = 0.002). INTERPRETATION: EEG burst suppression was associated with younger age, inhalation anesthetics, propofol bolus, and lower arterial pressure.

13.
J Int Med Res ; 49(11): 3000605211055624, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34775865

RESUMO

BACKGROUND: An appropriate electrolyte solution is important for safe intraoperative anesthesia management in children. This trial assessed the effectiveness of a novel 1% glucose isotonic electrolyte solution in intraoperative fluid therapy in children. METHODS: This trial analyzed data from 100 patients aged older than 1 month with an ASA score of I to II who received general anesthesia. Patients were randomly assigned to receive either the novel electrolyte solution (containing glucose, sodium, potassium, chloride, and bicarbonate) or lactated Ringer's solution intraoperatively as a maintenance fluid. Patient demographics and the results of blood gas analysis at 1, 2, and 3 hours were documented, and changes in glucose and electrolyte concentrations and the acid-base status were analyzed. RESULTS: During infusion of the novel solution, the glucose and potassium concentrations were stable. Conversely, the solution was linked to increased sodium levels but decreased bicarbonate levels, although both changes were within the physiological ranges. In addition, pH remained stable during the intraoperative period. Hypoglycemia, hyperglycemia, hyponatremia, or hypernatremia was not detected. CONCLUSIONS: The novel 1% glucose isotonic electrolyte solution helped to maintain glucose and electrolyte concentrations and acid-base stability, and it may therefore improve children's safety during the intraoperative period.


Assuntos
Glicemia , Glucose , Idoso , Criança , Eletrólitos , Hidratação , Humanos , Soluções Isotônicas
14.
Front Genet ; 12: 803257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35237295

RESUMO

Glioblastoma (GBM), originating in the brain, is a universally aggressive malignant tumor with a particularly poor prognosis. Therefore, insight into the critical role of underlying genetic mechanisms is essential to developing new therapeutic approaches. This study aims to identify potential markers with clinical and prognostic significance in GBM. To this end, increasing numbers of differentially expressed RNA have been identified used to construct competitive endogenous RNA networks for prognostic analysis via comparison and analysis of RNA expression levels of tumor and normal tissues in glioblastoma. This analysis demonstrated that the RNA expression patterns of normal and tumor samples were significantly different. Thus, the resulting differentially expressed RNAs were used to construct competitive endogenous RNA (competing endogenous RNA, ceRNA) networks. The functional enrichment indicated mRNAs in the network are critically involved in a variety of biological functions. Additionally, the prognostic analysis suggested 27 lncRNAs, including LOXL1-AS1, AL356414.1, etc., were significantly associated with patient survival. Given the prognostic significance of these 27 lncRNAs in GBM, we sought to classify the samples. Importantly, Kaplan-Meier analysis revealed that survival times varied significantly among the different categories. Overall, these results identify that the candidate lncRNAs are potential prognostic markers of GBM and its corresponding mRNAs may be a potential target for therapy.

15.
Neurosci Bull ; 36(6): 682, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32377989

RESUMO

The original version of this article unfortunately contained a mistake.

16.
Sci Rep ; 7(1): 7661, 2017 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-28794417

RESUMO

The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis.


Assuntos
Barreira Hematoencefálica/metabolismo , Estresse do Retículo Endoplasmático , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/metabolismo , Junções Aderentes/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Butilaminas/farmacologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/diagnóstico , Modelos Animais de Doenças , Progressão da Doença , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Peróxido de Hidrogênio/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/patologia , Pericitos/efeitos dos fármacos , Pericitos/metabolismo , Pericitos/patologia , Proteólise , Ratos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Junções Íntimas/metabolismo
17.
Oncotarget ; 8(19): 31638-31654, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28404943

RESUMO

Hypoxic-ischemic and inflammatory (HII) induces the disruption of blood-brain barrier (BBB) which leads to inflammatory responses and neuronal cell death, resulting in brain secondary damage. Previous studies showed that melatonin produced potent neuroprotective effects in neonatal hypoxic-ischaemic models. However, the relationship between BBB disruption and melatonin in HII was still unclear. The present study therefore investigated the beneficial effects of melatonin on BBB after HII and the underlying mechanisms. HII animal model was conducted by receiving lipopolysaccharide followed by 90 min hypoxia-ischaemia in postnatal day 2 Sprague-Dawley rat pups. Melatonin was injected intraperitoneally 1 h before lipopolysaccharide injection and then once a day for 1 week to evaluate the long-term effects. In this study, we demonstrated that melatonin administration inhibited the disruption of BBB permeability and improved the white matter recovery in HII model rats. Melatonin significantly attenuated the degradation of junction proteins and the neuroprotective role was related to the inhibition of microglial toll-like receptor 4/ nuclear factor-kappa B signaling pathway both in vivo and in vitro. Taken together, our data demonstrated that therapeutic strategies targeting inflammation might be suitable for the therapy of preserving BBB integrity after HII.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Melatonina/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/imunologia , Junções Aderentes/metabolismo , Animais , Animais Recém-Nascidos , Barreira Hematoencefálica/patologia , Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Modelos Animais de Doenças , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Lipopolissacarídeos/efeitos adversos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Biológicos , Pericitos/citologia , Pericitos/metabolismo , Permeabilidade , Ratos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Receptor 4 Toll-Like/metabolismo , Substância Branca/efeitos dos fármacos , Substância Branca/metabolismo , Substância Branca/patologia
18.
Nanoscale ; 8(29): 14222-36, 2016 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-27396404

RESUMO

Multifunctional nanoparticles capable of the specific delivery of therapeutics to diseased cells and the real-time imaging of these sites have the potential to improve cancer treatment through personalized therapy. In this study, we have proposed a multifunctional nanoparticle that integrate magnetic targeting, drug-carrier functionality and real-time MRI imaging capabilities in one platform for the theranostic treatment of tumors. The multifunctional nanoparticle was designed with a superparamagnetic iron oxide core and a multifunctional shell composed of PEG/PEI/polysorbate 80 (Ps 80) and was used to encapsulate DOX. DOX-loaded multifunctional nanoparticles (DOX@Ps 80-SPIONs) with a Dh of 58.0 nm, a zeta potential of 28.0 mV, and a drug loading content of 29.3% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 24.1 emu g(-1). The cellular uptake of DOX@Ps 80-SPIONs by C6 cells under a magnetic field was significantly enhanced over that of free DOX in solution, resulting in stronger in vitro cytotoxicity. The real-time therapeutic outcome of DOX@Ps 80-SPIONs was easily monitored by MRI. Furthermore, the negative contrast enhancement effect of the nanoparticles was confirmed in glioma-bearing rats. Prussian blue staining and ex vivo DOX fluorescence assays showed that the magnetic Ps 80-SPIONs and encapsulated DOX were delivered to gliomas by imposing external magnetic fields, indicating effective magnetic targeting. Due to magnetic targeting and Ps 80-mediated endocytosis, DOX@Ps 80-SPIONs in the presence of a magnetic field led to the complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism of DOX@Ps 80-SPIONs acted by inducing apoptosis through the caspase-3 pathway. Finally, DOX@Ps 80-SPIONs' safety at therapeutic dosage was verified using pathological HE assays of the heart, liver, spleen, lung and kidney. Multifunctional SPIONs could be used as potential carriers for the theranostic treatment of CNS diseases.

19.
Zhong Yao Cai ; 38(3): 567-71, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26495661

RESUMO

OBJECTIVE: To study the pharmacodynamics of Gualou Xiebai Dropping Pills and its medicinal ingredients in prescription on anti-myocardial ischemia. METHODS: SPF Rats were divided randomly into eleven groups with ten rats in each group and half male and half female, the rats were respectively given the physiological saline(blank group and model group), Gualou, Xiebai, Gualou Xiebai Baijiutang (all equivalent to the crude herb of 22. 5 g/kg), Gualou Xiebai. Dropping Pills in the doses of 3. 75,11. 25,22. 5,33. 75 and 45 g/kg and Compound Danshen Drop Pills of 0. 085 g/kg by gavage one time a day for seven days. Except blank group, other rats were given by intraperitoneal injection of isoproterenol to establish myocardial ischemia models, changes of ST segments in ECG were observed in all groups, and the levels of SOD, NO, HDL-C, MDA, CAT, LDH and CK in blood plasma were detected, and the pathological changes of myocardial tissues were observed under light microscope by HE staining. RESULTS: Compared with model group, ST segments in ECG dropped markedly at different time point which included 10,11 and 12 (P <0. 05) in Gualou Xiebai Drop Pills groups of 22. 5, 33. 75 and 45 g/kg, time points were more than those of other groups. Gualou Xiebai Dropping Pills groups of 22. 5 and 33. 75 g/kg improved the levels of SOD, MDA, CAT, NO, HDL-C, LDH and CK in blood plasma in model rats significantly (P <0. 01 or P <0. 05). Gualou Xeibai Dropping Pills improved the pathological changes of myocardial tissues at all dosages. CONCLUSION: Gualou Xiebai Drop Pills can effectively restrain the acute myocardial ischemia induced by isoproterenol in rats, compared with Gualou, Xiebai or Gualou Xiebai Baijiutang, Gualou Xiebai Drop Pills obtains a favourable effect.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Miocárdio/patologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Ratos , Salvia miltiorrhiza
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