RESUMO
OBJECTIVE: To observe the sensitivity of stroke volume variation (SVV) for assessing volume change during induction period of general anesthesia. METHODS: Patients who underwent orthopaedic surgery under general anesthesia and mechanical ventilation were divided into two groups randomly. Patients in the group â were subjected to progressive central hypovolemia and correction of hypovolemia sequentially; patients in the Group â ¡ were exposed to hypervolemia alone. Each step was implemented after 5 minutes when the hemodynamics was stable. SVV and cardiac index (CI) were recorded, and Pearson's product-moment correlation was used to analyze correlation between SVV and CI. RESULTS: Forty patients were included in this study, 20 cases in each group. For group â patients, SVV was increased significantly along with blood volume reduction, and changes in CI were negatively correlated with changes in SVV (r=-0.605, P<0.01); SVV decreased significantly along with correction of blood volume; changes in CI were negatively correlated with changes in SVV (r=-0.651, P<0.01). For group â ¡ patients, along with blood volume increase, SVV did not change significantly; changes in CI revealed no significant correlation with changes in SVV (r=0.067, P>0.05). CONCLUSION: SVV is a useful indicator for hypovolemia, but not for hypervolemia.
Assuntos
Pressão Arterial , Débito Cardíaco , Volume Sistólico , Adulto , Idoso , Volume Sanguíneo , Pressão Venosa Central , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período PerioperatórioRESUMO
Aim: This study used machine learning methods to develop a prediction model for knee pain in middle-aged and elderly individuals. Methods: A total of 5386 individuals above 45 years old were obtained from the National Health and Nutrition Examination Survey. Participants were randomly divided into a training set and a test set at a 7 : 3 ratio. The training set was used to create a prediction model, whereas the test set was used to validate the proposed model. We constructed multiple predictive models based on three machine learning methods: logistic regression, random forest, and Extreme Gradient Boosting. The model performance was evaluated by areas under the receiver (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. Additionally, we created a simplified nomogram based on logistic regression for better clinical application. Results: About 31.4% (1690) individuals were with self-reported knee pain. The logistic regression showed that female gender (odds ratio [OR] = 1.28), pain elsewhere (OR = 4.64), and body mass index (OR = 1.05) were significantly associated with increased risk of knee pain. In the test set, the logistic regression (AUC = 0.71) showed similar but slightly higher accuracy than the random forest (AUC = 0.70), while the performance of the Extreme Gradient Boosting model was less reliable (AUC = 0.59). Based on mean decrease accuracy, the most important first five predictions were pain elsewhere, waist circumference, body mass index, age, and gender. Additionally, the most important first five predictions with the highest mean decrease Gini index were pain elsewhere, body mass index, waist circumference, triglycerides, and age. The nomogram model showed good discrimination ability with an AUC of 0.75 (0.73-0.77), a sensitivity of 0.72, specificity of 0.71, a positive predictive value of 0.45, and a negative predictive value of 0.88. Conclusion: This study proposed a convenient nomogram tool to evaluate the risk of knee pain for the middle-aged and elderly US population in primary care. All the input variables can be easily obtained in a clinical setting, and no additional radiologic assessments were required.
Assuntos
Aprendizado de Máquina , Dor , Idoso , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Dor/diagnóstico , Dor/etiologia , TriglicerídeosRESUMO
OBJECTIVE: To compare the effects of gabapentin on high-voltage-activated calcium (HVA) current in dorsal root ganglion (DRG) neurons in normal and nerve-injured rats and understand the reasons of their differences. METHODS: Pathogen-free male SD rats (weight 180 - 220 mg) aged 4 - 6 weeks were used. The animals were anesthetized with intraperitoneal pentobarbital sodium 50 mg/kg. L(5) spinal nerve was ligated between DRG and sciatic nerve and cut distal to the ligature. The animals were decapitated at Day 14 post-operation. L(5) (SNL-L(5) group) and L(4) DRGs (SNL-L(4) group) were respectively isolated and the ganglionic neurons enzymatically dissociated. The control group of rats was not operated. The lumbar DRG neurons of normal rats were treated similarly. The HVA-Ca(2+) current was recorded by the technique of whole cell patch clamp. RESULTS: Compared with the SNL-L(4) group [(16.0 ± 1.9)%, (26.9 ± 2.0)%, (27.4 ± 2.3)%] and the control group, gabapentin inhibited the peak calcium current highlier at 10, 100 and 300 µmol/L in the SNL-L(5) group [(18.5 ± 1.7)%, (32.0 ± 2.6)%, (32.7 ± 2.8)%] (P < 0.05). The steady-state inactivation curves shifted to more hyperpolarized potentials in the SNL-L(5) group. The N-type relative contribution to the gabapentin-sensitive HVA-Ca(2+) current was markedly elevated in the SNL-L(5) group compared with that in other two groups (P < 0.05). CONCLUSION: Gabapentin enhances the inhibition of HVA-Ca(2+) current in injured DRG neurons following spinal nerve ligation in rats. The alteration in the activation of electrophysiological properties and the increase of N-type relative contribution to the total HVA-Ca(2+) current may be involved in the mechanism.
Assuntos
Aminas/farmacologia , Canais de Cálcio Tipo N/efeitos dos fármacos , Ácidos Cicloexanocarboxílicos/farmacologia , Gânglios Espinais/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Animais , Canais de Cálcio Tipo N/fisiologia , Células Cultivadas , Gabapentina , Gânglios Espinais/fisiologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-DawleyRESUMO
Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.
Assuntos
Neoplasias do Colo/metabolismo , Neoplasias Colorretais/metabolismo , Farnesil-Difosfato Farnesiltransferase/metabolismo , Jejum/psicologia , Glicólise/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Farnesil-Difosfato Farnesiltransferase/genética , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Transdução de Sinais/genéticaRESUMO
AIM: To investigate the effect of ginsenoside Rg1 on the migration, adhesion, proliferation, and VEGF expression of endothelial progenitor cells (EPCs). METHODS: EPCs were isolated from human peripheral blood and incubated with different concentrations of ginsenoside Rg1 (0.1, 0.5, 1.0, and 5.0 micromol/L) and vehicle controls. EPC migration was detected with a modified Boyden chamber assay. EPC adhesion was determined by counting adherent cells on fibronectin-coated culture dishes. EPC proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro vasculogenesis was assayed using an in vitro vasculogenesis detection kit. A VEGF-ELISA kit was used to measure the amount of VEGF protein in the cell culture medium. RESULTS: Ginsenoside Rg1 promoted EPC adhesion, proliferation, migration and in vitro vasculogenesis in a dose- and time-dependent manner. Cell cycle analysis showed that 5.0 micromol/L of ginsenoside Rg1 significantly increased the EPC proliferative phase (S phase) and decreased the resting phase (G(0)/G(1) phase). Ginsenoside Rg1 increased vascular endothelial growth factor production. CONCLUSION: The results indicate that ginsenoside Rg1 promotes proliferation, migration, adhesion and in vitro vasculogenesis.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Ginsenosídeos/farmacologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologia , Animais , Adesão Celular/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Fármacos do Sistema Nervoso Central/farmacologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/citologia , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Células-Tronco/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Several previous studies have demonstrated the excellent antioxidant activity of fucoxanthin against oxidative stress which is closely related to the pathogenesis of liver diseases. The present work was to investigate whether fucoxanthin could protect human hepatic L02 cells against hydrogen peroxide- (H2O2-) induced oxidative damage. Its effects on H2O2-induced cell viability, lactate dehydrogenase (LDH) leakage, intracellular reduced glutathione, and reactive oxygen species (ROS) contents, along with mRNA and protein relative levels of the cytoprotective genes including Nrf2, HO-1, and NQO1, were investigated. The results showed that fucoxanthin could upregulate the mRNA and protein levels of the cytoprotective genes and promote the nuclear translocation of Nrf2, which could be inhibited by the PI3K inhibitor of LY294002. Pretreatment of fucoxanthin resulted in decreased LDH leakage and intracellular ROS content but enhanced intracellular reduced glutathione. Interestingly, pretreatment using fucoxanthin protected against the oxidative damage in a nonconcentration-dependent manner, with fucoxanthin of 5 µM demonstrating the optimal effects. The results suggest that fucoxanthin exerts cytoprotective effects against H2O2-induced oxidative damage in L02 cells, which may be through the PI3K-dependent activation of Nrf2 signaling.
Assuntos
Citoproteção/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Xantofilas/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Glutationa/metabolismo , Heme Oxigenase-1/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Morfolinas/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: To observe the effects of ketamine on bronchial hyperresponsiveness and airway inflammation in equal asthma. METHODS: 56 Brown-Norway rats were randomly assigned to seven groups: negative control group (Group A), asthma model group (Group B) and inhalation groups with nebulized ketamine at different concentrations (Group C, D, E) and intraperitoneal injection groups with ketamine at different doses (Group F, G). The rats were sensitized by injection of ovalbumin (OVA) together with aluminum hydroxide and Bordetella pertussis as adjuvants, then challenged by repeated intermittent (thrice weekly) exposure to aerosolized OVA for two weeks. Before challenge, the sensitized rats were exposed to an aerosol of phosphate buffered saline (PBS) or ketamine at the concentrations of 12.5 mg/ml, 25 mg/ml and 50 mg/ml respectively in Groups B, C, D and E. The sensitized rats were intraperitoneally injected with ketamine at the doses of 50 microg/kg or 100 microg/kg respectively in Group F and G. The sensitized rats in Group A received phosphate buffered solution (PBS) by inhalation. The airway reactivity to acetylcholine (ACH) was assessed in vivo 24 hr after the last OVA challenge, then the lungs were removed for measurement of the mRNA and protein expression of iNOS and production of NO and lung sections for histopathologic examination. RESULTS: (1) In the OVA-sensitized and challenged rats, the dose-response curve of the expiratory resistance (Re) shifted to the upper-left +/- ward compared with that of PBS control rats. In addition, the provocation doses required to increase the Re by 100%, 200% and 400% for OVA-sensitized and challenged rats in Group B were significantly lower than those of the PBS control rats (14.65 +/- 1.19 vs 32.28 +/- 1.43, 15.17 +/- 1.19 vs 38.91 +/- 1.39, and 16.28 +/- 1.18 vs 56.53 +/- 1.38, all P < 0.01). The OVA-sensitized rats treated with ketamine before OVA challenge demonstrated a significant decrease in AHR by a rightward shift of the dose-response curves to ACH and significant higher provocation doses compared with that of the OVA control rats (P < 0.05). (2) Marked inflammatory changes in the airways of Group B were present, while obviously lessen inflammatory cell infiltration in peribronchial and perialveolar tissues and improved lung edema were observed in the groups treated with ketamine. (3) Quantitation by densitometry showed that the relative density of iNOS mRNA bands normalized to beta-actin was significantly higher in the OVA control than the PBS control (1.0 +/- 0.07 vs 0.48 +/- 0.07, P < 0.01). Treatment with ketamine significantly decreased the expression of iNOS mRNA in Group C (0.65 +/- 0.07), Group D (0.58 +/- 0.09), Group E (0.56 +/- 1.00), and Group F (0.66 +/- 0.06) when compared with Group B (all P < 0.05). (4) The relative iNOS protein levels (ratios of iNOS/beta-actin) determined by densitometry analysis showed a 4-fold increase in Group A compared with those in the negative group (0.54 +/- 0.08 vs 0.13 +/- 0.08, P < 0.05). When compared with those of the OVA control, the levels of relative iNOS protein expression showed a significant decrease in the lungs from the rats treated with ketamine inhalation at the doses of 12.5 mg/ml (0.20 +/- 0.03) and 25 mg/ml (0.18 +/- 0.03) and with ketamine and intraperitoneally the at dose of 50 microg/kg (0.21 +/- 0.04) (P < 0.05). (5) NO production in pulmonary tissues was significantly higher in the OVA-treated rats compared to the PBS controls (0.39 +/- 0.04 micromol/g protein vs 0.13 +/- 0.01 micromol/g protein, P < 0.01), but this OVA-triggered NO production was significantly decreased by treatment with 12.5 and 25 mg/ml inhaled ketamine (0.19 +/- 0.03 micromol/g and 0.17 +/- 0.03 micromol/g, both P < 0.05) and 50 microg/kg i.p.-injected ketamine (0.16 +/- 0.04 micromol/g, P < 0.05) when compared with the OVA-treated rats. CONCLUSION: Both inhalation and systemic administration of ketamine attenuate inflammatory the lung injury and airway hyperreactivity of the OVA-induced asthma model. The protective effects of ketamine is achieved by inhibiting OVA-provoked over-expression of mRNA and protein of iNOS and reducing the production of NO in pulmonary tissues.
Assuntos
Asma/tratamento farmacológico , Hiper-Reatividade Brônquica/prevenção & controle , Bronquite/prevenção & controle , Ketamina/uso terapêutico , Resistência das Vias Respiratórias , Alérgenos/imunologia , Animais , Asma/imunologia , Asma/fisiopatologia , Western Blotting , Hiper-Reatividade Brônquica/imunologia , Hiper-Reatividade Brônquica/fisiopatologia , Bronquite/imunologia , Bronquite/fisiopatologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Injeções Intraperitoneais , Ketamina/administração & dosagem , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Endogâmicos BN , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)-induced sepsis in mice. Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 µg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin-eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.
Assuntos
Diterpenos do Tipo Caurano/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sepse/tratamento farmacológico , Animais , Contagem de Colônia Microbiana , Diterpenos do Tipo Caurano/farmacologia , Interleucina-6/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Peritônio/efeitos dos fármacos , Peritônio/microbiologia , Peritônio/patologia , Substâncias Protetoras/farmacologia , Sepse/sangue , Sepse/patologia , Análise de Sobrevida , Fator de Necrose Tumoral alfa/sangueRESUMO
Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) has a potential immunoregulatory role dependent on Toll-like receptors (TLRs). TLR2, associated with deleterious systemic inflammation, cardiac dysfunction, and acute kidney injury, acts synergistically in sepsis. The role of MFHAS1 in targeting TLR2 involved in sepsis has not been examined thus far. This study aimed to examine the relationship of MFHAS1 and sepsis, and the effect of MFHAS1 on the TLR2 signaling pathway. Blood samples were collected from eight sepsis patients after surgery and eight patients undergoing selective surgery to determine blood MFHAS1 levels. HEK 293 cells, RAW 264.7 macrophages and THP-1 monocytes were used to confirm the effect of MFHAS1 on TLR2 signaling pathway. Our study showed that blood MFHAS1 was significantly elevated in septic patients, and MFHAS1 was more increased in mononuclear cells from septic patients. Pam3CSK4 (TLR2 ligand) was found to induce MFHAS1 production in RAW 264.7 murine macrophages and THP-1 human monocytes in a time-dependent manner. MFHAS1 has dual effects on TLR2 signaling pathway and inflammation, i.e., inhibitory effect at 6 hours, and then stimulatory effect after 24 hours through the activation of TLR2/NF-κB signaling pathway, and MFHAS1 induced the phosphorylation of JNK and p38 after TLR2 stimulation.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Proteínas Oncogênicas/metabolismo , Sepse/metabolismo , Receptor 2 Toll-Like/metabolismo , Idoso , Animais , Western Blotting , Linhagem Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Células HEK293 , Humanos , Lipopeptídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/agonistasRESUMO
Here, we report a facile approach to grow graphene on Cu-Ni alloy NFs at a temperature as low as 450-500 °C, in which solid polystyrene (PS) carbon source and two-temperature-zone furnace were used to prepare graphene. The graphene coated Cu-Ni (designated as G-coated Cu-Ni) NFs were fully characterized by Raman spectra, XPS, FESEM and TEM. The G-coated Cu-Ni NFs exhibited excellent anti-oxidation, anti-corrosion and flexibility properties. The anti-corrosion of G-coated Cu-Ni NFs was examined through cyclic voltammetry measurements by using sea water as the electrolyte solution. Finally, using crossed arrays of G-coated Cu-Ni NF composite electrode thin films (sheet resistance is â¼10 Ω sq(-1)) as the flexible electrode, an alternating current (AC) electroluminescent (EL) device with a configuration of G-coated Cu-Ni/active layer (ZnS : Cu phosphor)/dielectric layer (BaTiO3)/front electrode (CNT) has been fabricated. Under an AC voltage of 200 V and frequency of 1300 Hz, the ACEL device emitted blue light at 496 nm with a brightness of 103 cd m(-2).
RESUMO
Since airway hyperresponsiveness (AHR) and allergic inflammatory changes are regarded as the primary manifestations of asthma, the main goals of asthma treatment are to decrease inflammation and maximize bronchodilation. These goals can be achieved with aerosol therapy. Intravenous administration of the anesthetic, ketamine, has been shown to trigger bronchial smooth muscle relaxation. Furthermore, increasing evidence suggests that the anti-inflammatory properties of ketamine may protect against lung injury. However, ketamine inhalation might yield the same or better results at higher airway and lower ketamine plasma concentrations for the treatment of asthma. Here, we studied the effect of ketamine inhalation on bronchial hyperresponsiveness and airway inflammation in a Brown-Norway rat model of ovalbumin (OVA)-induced allergic asthma. Animals were actively sensitized by subcutaneous injection of OVA and challenged by repeated intermittent (thrice weekly) exposure to aerosolized OVA for two weeks. Before challenge, the sensitized rats received inhalation of aerosol of phosphate-buffered saline (PBS) or aerosol of ketamine or injection of ketamine respectivity. Airway reactivity to acetylcholine (Ach) was measured in vivo, and various inflammatory markers, including Th2 cytokines in bronchoalveolar lavage fluid (BALF), as well as inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in lungs were examined. Our results revealed that delivery of aerosolized ketamine using an ultrasonic nebulizer markedly suppressed allergen-mediated airway hyperreactivity, airway inflammation and airway inflammatory cell infiltration into the BALF, and significantly decreased the levels of interleukin-4 (IL-4) in the BALF and expression of iNOS and the concentration of NO in the inflamed airways from OVA-treated rats. These findings collectively indicate that nebulized ketamine attenuated many of the central components of inflammatory changes and AHR in OVA-provoked experimental asthma, potentially providing a new therapeutic approach against asthma.