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1.
Acta Chim Slov ; 69(2): 385-392, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35861081

RESUMO

A series of hydrazones, 2-cyano-N'-(4-diethylamino-2-hydroxybenzylidene)acetohydrazide (1), N'-(5-bromo-2-hydroxy-3-methoxybenzylidene)-3-chlorobenzohydrazide monohydrate (2·H2O), N'-(2-hydroxy-3-methylbenzylidene)-4-nitrobenzohydrazide (3), and N'-(2-hydroxy-3-trifluoromethoxybenzylidene)-4-nitrobenzohydrazide (4), were prepared and structurally characterized by elemental analysis, IR and 1H NMR spectra, and single crystal X-ray determination. Xanthine oxidase inhibitory activities of the compounds were studied. Among the compounds, 2-cyano-N'-(4-diethylamino-2-hydroxybenzylidene)acetohydrazide shows the most effective activity. Docking simulation was performed to insert the compounds into the crystal structure of xanthine oxidase at the active site to investigate the probable binding modes.


Assuntos
Hidrazonas , Xantina Oxidase , Domínio Catalítico , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Xantina Oxidase/metabolismo
2.
Exp Brain Res ; 240(5): 1435-1444, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35333956

RESUMO

The relieving role of dezocine in pain after surgery was previously reported, while the potential mechanism was not completely clear. Therefore, the current research probed into the regulatory mechanism of dezocine in pain after surgery. A postoperative pain model was established by performing plantar incision surgery on the juvenile Sprague-Dawley rats. After the rats were treated with dezocine or SC79 (Akt1 activator), the paw withdrawal threshold and paw withdrawal latency of rats were detected to evaluate the mechanical allodynia and thermal hyperalgesia. After the plantar tissue, dorsal root ganglions, and spinal cord of rats were collected, the expressions of Akt1, p-Akt1, GSK-3ß, and p-GSK-3ß in the tissues were determined by western blot to evaluate the activation state of the Akt1/GSK-3ß pathway. After surgery, the paw withdrawal threshold and paw withdrawal latency of rats were lessened, whereas the ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß were augmented in rat plantar tissue, dorsal root ganglions, and spinal cord. After treatment with dezocine alone, the paw withdrawal threshold and paw withdrawal latency of postoperative rats were elevated, but ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß were reduced. After co-treatment with dezocine and SC79, SC79 reversed the effects of dezocine on elevating the paw withdrawal threshold and paw withdrawal latency, and reducing the ratios of p-Akt1/Akt1 and p-GSK-3ß/GSK-3ß in postoperative rats. Dezocine ameliorated the postoperative hyperalgesia in rats via repressing the hyper-action of Akt1/GSK-3ß pathway.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Hiperalgesia , Dor Pós-Operatória , Tetra-Hidronaftalenos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Glicogênio Sintase Quinase 3 beta , Hiperalgesia/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/metabolismo , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Tetra-Hidronaftalenos/farmacologia
3.
Med Sci Monit ; 27: e930369, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34253706

RESUMO

BACKGROUND Fentanyl-induced cough (FIC) during general anesthesia induction and postoperative nausea and vomiting are common complications, yet the risk factors for FIC remain controversial. This retrospective study was conducted at a single center in China and aimed to investigate the risk factors for fentanyl-induced cough following general anesthesia in adults. MATERIAL AND METHODS A total of 601 adult patients undergoing elective surgery were enrolled, and the incidence of FIC during general anesthesia induction and postoperative adverse events were recorded. The risk factors for FIC during general anesthesia induction and postoperative nausea and vomiting were assessed using multivariate logistic regression analysis. RESULTS The incidence of FIC, nausea, and vomiting were 21.8%, 6.3%, and 4.5%, respectively. The results of multivariate logistic regression analysis indicated that pharyngitis history was associated with an increased risk of FIC during general anesthesia induction (odds ratio [OR]: 2.852; 95% confidence interval [CI]: 1.698-4.792; P<0.001), whereas use of lidocaine could protect against FIC risk (OR: 0.649; 95% CI: 0.557-0.757; P<0.001). However, the characteristics of patients were not associated with the risk of postoperative nausea and vomiting. CONCLUSIONS The findings from this study showed that a history of pharyngitis increased the risk of FIC, while the use of lidocaine was associated with a reduced risk of FIC. The risk of postoperative nausea and vomiting was not affected by fentanyl use or patient characteristics.


Assuntos
Adjuvantes Anestésicos/efeitos adversos , Anestesia Geral , Tosse/induzido quimicamente , Fentanila/efeitos adversos , Administração Intravenosa , Adulto , Anestésicos Intravenosos , Procedimentos Cirúrgicos Eletivos , Humanos , Incidência , Lidocaína , Pessoa de Meia-Idade , Razão de Chances , Náusea e Vômito Pós-Operatórios , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
World J Clin Cases ; 9(35): 10861-10870, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-35047597

RESUMO

BACKGROUND: Gastroesophageal reflux (GER) affects up to 20% of the adult population and is defined as troublesome and frequent symptoms of heartburn or regurgitation. GER produces significantly harmful impacts on quality of life and precipitates poor mental well-being. However, the potential risk factors for the incidence and extent of GER in adults undergoing general anesthesia remain unclear. AIM: To explore independent risk factors for the incidence and extent of GER during general anesthesia induction. METHODS: A retrospective study was conducted, and 601 adult patients received general anesthesia intubation or laryngeal mask surgery between July 2016 and January 2019 in Shanghai General Hospital of Nanjing Medical University. This study recruited a total of 601 adult patients undergoing general anesthesia, and the characteristics of patients and the incidence or extent of GER were recorded. The potential risk factors for the incidence of GER were explored using multivariate logistic regression, and the risk factors for the extent of GER were evaluated using multivariate linear regression. RESULTS: The current study included 601 adult patients, 82 patients with GER and 519 patients without GER. Overall, we noted significant differences between GER and non-GER for pharyngitis, history of GER, other digestive tract diseases, history of asthma, and the use of sufentanil (P < 0.05), while no significant differences between groups were observed for sex, age, type of surgery, operative time, body mass index, intraoperative blood loss, smoking status, alcohol intake, hypertension, diabetes mellitus, psychiatric history, history of respiratory infection, history of surgery, the use of lidocaine, palliative strategies, propofol, or rocuronium bromide, state anxiety inventory, trait anxiety inventory, and self-rating depression scale (P > 0.05). The results of multivariate logistic regression indicated that female sex [odds ratio (OR): 2.702; 95% confidence interval (CI): 1.144-6.378; P = 0.023], increased age (OR: 1.031; 95%CI: 1.008-1.056; P = 0.009), pharyngitis (OR: 31.388; 95%CI: 15.709-62.715; P < 0.001), and history of GER (OR: 11.925; 95%CI: 4.184-33.989; P < 0.001) were associated with an increased risk of GER, whereas the use of propofol could protect against the risk of GER (OR: 0.942; 95%CI: 0.892-0.994; P = 0.031). Finally, age (P = 0.004), operative time (P < 0.001), pharyngitis (P < 0.001), history of GER (P = 0.024), and hypertension (P = 0.017) were significantly associated with GER time. CONCLUSION: This study identified the risk factors for GER in patients undergoing general anesthesia including female sex, increased age, pharyngitis, and history of GER.

5.
Oxid Med Cell Longev ; 2020: 1720961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765805

RESUMO

Sepsis-induced diaphragm dysfunction (SIDD) which is mainly characterized by decrease in diaphragmatic contractility has been identified to cause great harms to patients. Therefore, there is an important and pressing need to find effective treatments for improving SIDD. In addition, acetylcholinesterase (AChE) activity is a vital property of the diaphragm, so we evaluated both diaphragmatic contractility and AChE activity. Though neuregulin-1ß (NRG-1ß) is known to exert organ-protective effects in some inflammatory diseases, little is known about the potential of NRG-1ß therapy in the diaphragm during sepsis. Our study was aimed at exploring the effects of NRG-1ß application on diaphragmatic contractility and AChE activity during sepsis. Proinflammatory cytokines, muscle injury biomarkers in serum, contractile force, AChE activity, proinflammatory cytokines, oxidative parameters, histological condition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and expression of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt) signaling proteins in the diaphragm were measured and compared between nonseptic and septic groups with or without NRG-1ß treatment. In vitro, the effects of NRG-1ß on reactive oxygen species (ROS) production in the lipopolysaccharide- (LPS-) stimulated L6 rat muscle skeletal cells with or without the Akt inhibitor MK-2206 were detected. NRG-1ß inhibited proinflammatory cytokine release and muscle injury biomarkers soaring in serum and improved the sepsis-induced diaphragm dysfunction and AChE activity decrease significantly during sepsis. Meanwhile, the inflammatory response, oxidative stress, pathological impairment, and cell apoptosis in the diaphragm were mitigated by NRG-1ß. And NRG-1ß activated the PI3K/Akt signaling in the diaphragm of septic rats. Elevated ROS production in the LPS-stimulated L6 rat skeletal muscle cells was reduced after treatment with NRG-1ß, while MK-2206 blocked these effects of NRG-1ß. In conclusion, our findings underlined that NRG-1ß could reduce circulating levels of proinflammatory cytokines in rats with sepsis, adjust diaphragmatic proinflammatory cytokine level, mitigate diaphragmatic oxidative injury, and lessen diaphragm cell apoptosis, thereby improving diaphragmatic function, and play a role in diaphragmatic protection by activating PI3K/Akt signaling.


Assuntos
Diafragma/efeitos dos fármacos , Neuregulina-1/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/tratamento farmacológico , Animais , Inflamação , Masculino , Neuregulina-1/farmacologia , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
6.
Cell Mol Neurobiol ; 39(7): 1029-1037, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31172341

RESUMO

Previous studies reported that RNA-binding protein human antigen R (HuR) mediates changes in the stability of AChR ß-subunit mRNA after skeletal muscle denervation; also, p38 pathway regulated the stability of AChR ß-subunit mRNA in C2C12 myotubes. However, the relationship between HuR and p38 in regulating the stability of AChR ß-subunit mRNA have not been clarified. In this study, we wanted to examine the effect of inhibiting p38 on HuR in denervated skeletal muscle. Denervation model was built and 10% DMSO or SB203580 were administered respectively follow denervation. Tibialis muscles were collected in 10% DMSO-administered contralateral (undenervated) leg, 10% DMSO-administered denervated leg, SB203580-administered contralateral (undenervated) leg, and SB203580-administered denervated leg, respectively. P38 protein, ß-AChR mRNA and protein, HuR protein, ß-AChR mRNA stability, and HuR binding with AChR ß-subunit mRNAs were measured. Results demonstrated that the administration of SB203580 can inhibit the increase of ß-AChR protein expression and mRNA expression and stability, and RNA-binding protein human antigen R (HuR) expression, in cytoplasmic and nuclear fractions in skeletal muscle cells following denervation. Importantly, we observed that SB203580 also inhibited the increased level of binding activity between HuR and AChR ß-subunit mRNAs following denervation. Collectively, these results suggested that inhibition of p38 can post-transcriptionally inhibit ß-AChR upregulation via HuR in denervated skeletal muscle.


Assuntos
Proteína Semelhante a ELAV 1/metabolismo , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Receptores Nicotínicos/metabolismo , Transcrição Gênica , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Ativação Enzimática/efeitos dos fármacos , Extremidades/inervação , Imidazóis/farmacologia , Masculino , Camundongos , Denervação Muscular , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Piridinas/farmacologia , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Receptores Nicotínicos/genética , Transcrição Gênica/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
J Muscle Res Cell Motil ; 40(1): 43-51, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30989579

RESUMO

The aim of this study was to investigate the protective effects of neuregulin-1ß (NRG-1ß) on sepsis-induced diaphragm atrophy and the possible underlying mechanisms. Sprague-Dawley rats were randomly divided into sham, sepsis and NRG groups. Sepsis was induced by cecal ligation and puncture (CLP). In the NRG group, rats received tail vein injections of NRG-1ß (10 µg/kg) every 12 h for 72 h after CLP. At 3 days after surgery, diaphragm contractile forces were measured by determining the force-frequency curve and muscle fiber areas by hematoxylin-eosin staining. Moreover, the NRG-1 expression level in the diaphragm was detected by Western blotting. Furthermore, the proteins in the PI3K/Akt signaling pathway and its downstream Akt-mTOR and Akt-FOXO axes were detected by Western blotting analysis. In L6 myotubes treated with lipopolysaccharide (LPS) and NRG-1ß, PI3K/Akt signaling pathway-related protein expression was further determined using the PI3K inhibitor LY294002. Exogenous NRG-1ß could compensate for sepsis-induced diminished NRG-1 in the diaphragm and attenuate the reduction in diaphragm contractile forces and muscle fiber areas during sepsis. Moreover, NRG-1ß treatment could activate the PI3K/Akt signaling pathway in the diaphragm during sepsis. The inhibition of p70S6K and 4E-BP1 on the Akt-mTOR axis and the increased expression of Murf1 on the Akt-FOXO axis were reversed after NRG-1 treatment. In addition, NRG-1ß could activate the PI3K/Akt signaling pathway in L6 myotubes treated with LPS, while the PI3K inhibitor LY294002 blocked the effects of NRG-1ß. NRG-1 expression in the diaphragm was reduced during sepsis, and exogenously administered recombinant human NRG-1ß could attenuate sepsis-induced diaphragm atrophy by activating the PI3K/Akt signaling pathway.


Assuntos
Diafragma/metabolismo , Atrofia Muscular/metabolismo , Neuregulina-1/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sepse/metabolismo , Transdução de Sinais , Animais , Cromonas/farmacologia , Diafragma/patologia , Diafragma/fisiopatologia , Modelos Animais de Doenças , Humanos , Masculino , Morfolinas/farmacologia , Contração Muscular/efeitos dos fármacos , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Neuregulina-1/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Sepse/patologia , Sepse/fisiopatologia
9.
Pharmacology ; 102(3-4): 190-195, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30099454

RESUMO

BACKGROUND/AIMS: Denervation resulted in resistance to non-depolarizing muscle relaxants (NDMRs), the magnitude of which changed after denervation in the skeletal muscle. The aim of this study was to investigate whether changed potencies of rocuronium were due to altered γ-acetylcholine receptor (γ-AChR) expression after skeletal muscle denervation. METHODS: Innervated and denervated muscle cells were used in this study. Patch clamp and Western blotting techniques were separately applied to examine IC50 values of rocuronium and γ-AChR protein expression at different times after denervation. Then, using the linear Pearson correlation analysis, the relationship between IC50 values of rocuronium and γ-AChR expression was tested. RESULTS: Compared with the innervated control, both IC50 values of rocuronium and γ-AChR expression significantly increased at Day 4, 7, and 14 after denervation in the skeletal muscle. Furthermore, γ-AChR protein and IC50 values of rocuronium exibited a significant positive correlation (r = 0.7678, p < 0.0001). CONCLUSION: These above results indicated that dynamic changes of resistance to NDMRs may be due to altered γ-AChR expression after skeletal muscle denervation.


Assuntos
Androstanóis/farmacologia , Músculo Esquelético/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Receptores Nicotínicos/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Denervação Muscular , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Técnicas de Patch-Clamp , Rocurônio
10.
Oxid Med Cell Longev ; 2017: 9718615, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230271

RESUMO

Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid-grade septic group than in the low-grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid-grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.


Assuntos
Acetilcolinesterase/metabolismo , Diafragma/patologia , Junção Neuromuscular/metabolismo , Sepse/complicações , Animais , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
11.
BMC Anesthesiol ; 17(1): 154, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29166854

RESUMO

BACKGROUND: Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. METHODS: A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. RESULTS: Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P < 0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2 ± 0.5 vs. 5.2 ± 0.6; P < 0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups. CONCLUSION: Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. TRIAL REGISTRATION: A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.


Assuntos
Período de Recuperação da Anestesia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Éteres Metílicos/administração & dosagem , Piperidinas/administração & dosagem , Complicações Pós-Operatórias/tratamento farmacológico , Agitação Psicomotora/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/efeitos adversos , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Éteres Metílicos/efeitos adversos , Piperidinas/efeitos adversos , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/diagnóstico , Estudos Prospectivos , Agitação Psicomotora/etiologia , Remifentanil , Sevoflurano
12.
Mol Med Rep ; 16(4): 5263-5268, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849127

RESUMO

Our previous study demonstrated that sepsis may decrease the activity of acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) of the diaphragm at 24 h, and thus improve the antagonistic action of neostigmine on rocuronium. The present study aimed to determine the effects of sepsis on AChE activity over 2 weeks, which is a more clinically relevant time period. Furthermore, the present study aimed to elucidate the association between AChE activity and its expression at the NMJ during sepsis. Male adult Sprague­Dawley rats were randomly divided into the sham or sepsis groups. Sepsis was induced by cecal ligation and puncture. On days 1, 3, 7 and 14 after surgery, AChE activity at the NMJ of the diaphragm was detected using a modified Karnovsky and Roots method. Furthermore, AChE expression levels at the NMJ, and in the whole muscle fibers of the diaphragm, were detected by immunohistofluorescence staining and western blot analysis, respectively. AChE activity was significantly decreased in the sepsis group, with its lowest level detected on day 7; however, its activity had partially recovered on day 14 (P<0.01). AChE activity was positively correlated (r=0.975, P=0.025) with its expression at the NMJ, which showed a similar trend over 2 weeks of sepsis. The protein expression levels of AChE in the whole muscle fibers of the diaphragm were significantly decreased on days 1, 3 and 7 in the sepsis group (P<0.01), with the lowest level observed on day 3. In conclusion, sepsis decreased AChE activity by reducing its expression at the NMJ over 14 days; the reduced expression of AChE at the NMJ might be as a result of its reduced muscular production.


Assuntos
Acetilcolinesterase/metabolismo , Junção Neuromuscular/enzimologia , Sepse/enzimologia , Sepse/patologia , Animais , Diafragma/enzimologia , Diafragma/patologia , Masculino , Fibras Musculares Esqueléticas/enzimologia , Fibras Musculares Esqueléticas/patologia , Ratos Sprague-Dawley
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 191-196, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28612525

RESUMO

OBJECTIVES: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis. METHODS: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively. Glucose levels and weight were observed weekly. Segments of aortoa of three groups were taken at 2, 4, 6 and 8 weeks, staining of senescent ß-galactosidase (SA-ß-gal) staining, HE and changes of aorta under light microscope were observed. The area of tunica intima (I) and tunica media (M) in aorta was measured, and their ratio (I/M) were analyzed. Expressions of gamma-histong family 2A variant (γ-H2AX), phosphorylated ataxia telangiectasia mutated (ATM), phosphorylated checkpoint kinasen 2 (CHK2) and phosphorylated P53 were detected by immunohistochemical staining. RESULTS: SA-ß-gal staining positive areas were dotted around in group B and group C [CM(155.3mm]but not in group A at two weeks.At the same time, a slight hyperlasia of aortic neointima was observed in HE staining of group B and group C. SA-ß-gal staining was positive scattered within the tunica intima of aorta of group B and group C at four weeks, and HE staining promted a significantly greater of aortic neointima in the group C than that in the other two group (P<0.05). Positive regions of SA-ß-gal staining were more in group C than group B at six weeks. Typical atherosclerotic plaques were formed, vascular smooth muscle cells were disordered arranged and foam cells were aggregated in the plaques of group C at six weeks post-operatively, and intimal membrane areas increased than group A and group B (P <0.05). At 8 weeks, SA-ß-gal positive areas in group C were greater than in group B. The arteriolar wall was markedly thickened and the lumen was narrowed. The area of intimal membrane and the I/M radio were significantly greater in group C than those in group A and group B (P <0.05). Positive expressed of γ-H2AX, phosphorylated ATM, phosphorylated CHK2 and phosphorylated P53 were observed in typical atherosclerotic foci of group C, and weaker expressed in group B. CONCLUSION: Cellular senescence of vascular edothelium is triggered and DNA double-strain damage is increased in diabetes. The DNA double-strain damage repairing machines may participate in the development of diabetic atherosclerosis.


Assuntos
Aterosclerose/genética , Dano ao DNA , Reparo do DNA , Diabetes Mellitus Experimental/genética , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Aterosclerose/patologia , Quinase do Ponto de Checagem 2/metabolismo , Diabetes Mellitus Experimental/patologia , Histonas/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Proteína Supressora de Tumor p53/metabolismo , Túnica Íntima
14.
Exp Ther Med ; 13(6): 2707-2714, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28587334

RESUMO

Previous studies have reported the incomplete relaxation effect of neuromuscular blockers on skeletal muscles in acute peritonitis (AP) and other inflammatory processes; however, the underlying mechanisms responsible for this effect have not yet been satisfactorily identified. The impaired removal of cytosolic Ca2+ through sarcoendoplasmic Ca2+-ATPase (SERCA) and defects in sarcoplasmic reticulum (SR) Ca2+ uptake are the major contributing factors to diastolic dysfunction. Previous studies on the effects of neuromuscular blockers have primarily focused on neuromuscular transmission. Because of the reduced calcium uptake in the SR itself, even when neuromuscular transmission is fully blocked, the muscle is not able to relax effectively. In the present study, the impact of AP on rocuronium-induced intraperitoneal pressure reduction and rectus abdominal muscle relaxation, and SERCA uptake function was investigated. AP was induced via gastric perforation and changes in the intraperitoneal pressure before and after the administration of rocuronium were recorded. Muscle contractile properties, uptake and release functions and SERCA activity in the rectus abdominal muscles of AP model rats were measured. The half-relaxation time in the AP group was significantly prolonged compared with that in the control group (P<0.01). The peak rate of SR Ca2+ uptake for whole muscle homogenates was significantly reduced (P<0.05) in AP model rats without reduction of the rate of Ca2+ release evoked through AgNO3. In conclusion, gastric perforation-induced AP attenuates the intraperitoneal pressure-reducing effect of rocuronium, and AP induces diastolic dysfunction of the rectus abdominal muscle. The SR Ca2+-ATPase uptake rate was also reduced by AP.

15.
J Biomech ; 52: 89-94, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28062122

RESUMO

The feasibility of computational fluid dynamics (CFD) to evaluate airflow characteristics in different head and neck positions has not been established. This study compared the changes in volume and airflow behavior of the upper airway by CFD simulation to predict the influence of anatomical and physiological airway changes due to different head-neck positions on mechanical ventilation. One awake volunteer with no risk of difficult airway underwent computed tomography in neutral position, extension position (both head and neck extended), and sniffing position (head extended and neck flexed). Three-dimensional airway models of the upper airway were reconstructed. The total volume (V) and narrowest area (Amin) of the airway models were measured. CFD simulation with an Spalart-Allmaras model was performed to characterize airflow behavior in neutral, extension, and sniffing positions of closed-mouth and open-mouth ventilation. The comparison result for V was neutral

Assuntos
Ar , Simulação por Computador , Cabeça/fisiologia , Hidrodinâmica , Pescoço/fisiologia , Postura , Fenômenos Fisiológicos Respiratórios , Adulto , Feminino , Humanos , Respiração Artificial
16.
Mol Med Rep ; 14(3): 2257-63, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27430244

RESUMO

The functional expression of recombinant α7 nicotinic acetylcholine receptors in human embryonic kidney (HEK) 293 cells has presented a challenge. Resistance to inhibitors of cholinesterase 3 (RIC­3) has been confirmed to act as a molecular chaperone of nicotinic acetylcholine receptors. The primary objectives of the present study were to investigate whether the co­expression of human (h)RIC­3 with human α7 nicotinic acetylcholine receptor in HEK 293 cells facilitates functional expression of the α7 nicotinic acetylcholine receptor. Subsequent to transfection, western blotting and polymerase chain reaction were used to test the expression of α7 nicotinic acetylcholine receptor and RIC-3. The α7 nicotinic acetylcholine receptor was expressed alone or co­expressed with hRIC­3 in the HEK 293 cells. Drug­containing solution was then applied to the cells via a gravity­driven perfusion system. Calcium influx in the cells was analyzed using calcium imaging. Nicotine did not induce calcium influx in the HEK 293 cells expressing human α7 nicotinic acetylcholine receptor only. However, in the cells co­expressing human RIC­3 and α7 nicotinic acetylcholine receptor, nicotine induced calcium influx via the α7 nicotinic acetylcholine receptor in a concentration­dependent manner (concentration required to elicit 50% of the maximal effect=29.21 µM). Taken together, the results of the present study suggested that the co­expression of RIC­3 in HEK 293 cells facilitated the functional expression of the α7 nicotinic acetylcholine receptor.


Assuntos
Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Membrana Celular/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Agonistas Nicotínicos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção , Receptor Nicotínico de Acetilcolina alfa7/genética
17.
Chin Med J (Engl) ; 129(12): 1477-82, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-27270546

RESUMO

BACKGROUND: The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP). METHODS: A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 µmol/L of neostigmine on Roc (10 µmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction. RESULTS: Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 µmol/L; P = 0.009 for 0.5 µmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET). CONCLUSIONS: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.


Assuntos
Androstanóis/farmacologia , Neostigmina/farmacologia , Sepse/fisiopatologia , Acetilcolinesterase/metabolismo , Animais , Ceco/lesões , Inibidores da Colinesterase/farmacologia , Diafragma/efeitos dos fármacos , Diafragma/metabolismo , Modelos Animais de Doenças , Ligadura , Masculino , Junção Neuromuscular/enzimologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Punções , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rocurônio
18.
Muscle Nerve ; 54(6): 1108-1113, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27104787

RESUMO

INTRODUCTION: The aim of this study was to study the effects of sepsis on diaphragm relaxation properties and the associated expression of sarco-endoplasmic reticulum Ca2+ -ATPase genes SERCA1 and SERCA2. METHODS: Rats were randomized to undergo either sham surgery or cecal ligation and puncture (CLP). Diaphragm isometric relaxation parameters were measured after 24 h. The mRNA expression and protein content of SERCA1 and SERCA2 in diaphragm muscles were determined. RESULTS: Both diaphragm maximal twitch and tetanus relaxation rates were reduced. Twitch half-relaxation time was prolonged after normalization to half of peak twitch tension. The mRNA expression and protein content of SERCA1 and SERCA2 were decreased. CONCLUSIONS: Slowed relaxation of the diaphragm in septic rats was associated with reduced expression of SERCA1 and SERCA2. Muscle Nerve 54: 1108-1113, 2016.


Assuntos
Diafragma/metabolismo , Diafragma/fisiopatologia , Regulação Enzimológica da Expressão Gênica/fisiologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Sepse/patologia , Animais , Cecostomia/efeitos adversos , Ceco/cirurgia , Modelos Animais de Doenças , Estimulação Elétrica , Técnicas In Vitro , Ligadura/efeitos adversos , Contração Muscular/fisiologia , RNA Mensageiro/metabolismo , Ratos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Sepse/etiologia
19.
J Surg Res ; 200(2): 637-47, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26507277

RESUMO

BACKGROUND: Intracellular calcium overload is a major contributing factor to diaphragmatic dysfunction triggered by sepsis. In this study, the possible role of dantrolene, a ryanodine receptor inhibitor, in preventing the release of calcium from the sarcoplasmic reticulum in diaphragmatic dysfunction and weakness was explored. METHODS: A middle-grade severity sepsis rat model was established for the effects of treatment with dantrolene, on diaphragm harvested 24 h after cecal ligation and puncture (CLP), and analyzed using functional, histologic, and biomarker assays. RESULTS: It was found that in septic rats, treatment with dantrolene significantly improved the contractility, relaxation, and fatigue index of the diaphragm in a dose-dependent manner. The benefits are associated with improvement in ultrastructural changes of Z band integrity and myofilament arrangements along with increases both in the ratio of slow-twitch type composition. Moreover, dantrolene effectively inhibits the overexpression of high-mobility group box 1 and reduces the calpain-1-caspase-3 proteolytic activity. CONCLUSIONS: Dantrolene can effectively attenuate the dysfunction of diaphragm in septic rats; Furthermore, the beneficial effects were associated with downregulation of high-mobility group box 1 and calpain-1-caspase-3 proteolytic activity.


Assuntos
Dantroleno/farmacologia , Diafragma/efeitos dos fármacos , Proteína HMGB1/metabolismo , Relaxantes Musculares Centrais/farmacologia , Proteólise/efeitos dos fármacos , Sepse/tratamento farmacológico , Animais , Biomarcadores/metabolismo , Calpaína/metabolismo , Caspase 3/metabolismo , Dantroleno/uso terapêutico , Diafragma/metabolismo , Diafragma/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sepse/metabolismo , Sepse/fisiopatologia
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(4): 438-443, 2016 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-28446393

RESUMO

OBJECTIVE: The explore the mechanism responsible for diaphragmatic contractile and relaxation dysfunction in a rat model of sepsis. METHODS: Thirty-six adult male Sprague-Dawley rats were randomized equally into a sham-operated group and two model groups of sepsis induced by cecal ligation and puncture (CLP) for examination at 6 and 12 h following CLP (CLP-6 h and CLP-12 h groups). The parameters of diaphragm contractile and relaxation were measured, and the calcium uptake and release rates of the diaphragmatic sarcoendoplasmic reticulum (SR) and the protein expressions of SERCA1, SERCA2 and RyR in the diaphragmatic muscles were determined. RESULTS: The half-relaxation time of the diaphragm was extended in both the CLP-6 h and CLP-12 h groups with significantly reduced maximum tension declinerate and the peek uptake rate of SERCA (P<0.01). Diaphragmatic maximum twitch force development rate, the maximal twitch, tetanus tensions and the peek release rate of SR decreased only at 12h after CLP (P<0.01). The expression levels of SERCA1 protein decreased significantly in the diaphragmatic muscles at 12h following CLP (P<0.01) while SERCA2 expression level and SERCA activity showed no significant changes. CONCLUSION: In the acute stage of sepsis, both the contractile and relaxation functions of the diaphragm are impaired. Diaphragmatic relaxation dysfunction may result from reduced calcium uptake in the SR and a decreased level of SERCA1 in the diaphragmatic muscles.


Assuntos
Cálcio/metabolismo , Diafragma/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Contração Muscular/efeitos dos fármacos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Retículo Sarcoplasmático/metabolismo , Animais , Ceco , Diafragma/metabolismo , Ligadura , Masculino , Ratos , Ratos Sprague-Dawley , Sepse
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