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AIM: To investigate the mechanism of the radiosensitizing effect of maximum non-cytotoxic doses of tetrandrine (Tet) on nasopharyngeal carcinoma cell lines CNE1 and CNE2.METHODS: The cells were treated with ma-ximum non-cytotoxic doses of Tet (for CNE1 cells at 1.5 μmol/L and for CNE2 cells at 1.8 μmol/L), irradiation at 4 Gy, or combination of irradiation and maximum non-cytotoxic doses of Tet. The cell cycle distribution was analyzed by flow cytometry. The protein levels of γ-H2AX, cleaved caspase-3, p-CDC25C, CDK1, p-CDK1, cyclin B1, ERK and p-ERK were determined by Western blot.RESULTS: The expression of γ-H2AX was increased in CNE1 cells and CNE2 cells after combined treatment with irradiation and maximum non-cytotoxic doses of Tet. The percentages of CNE1 cells and CNE2 cells at G2/M phase in irradiation group were (18.09±0.42)% and (18.48±1.32)%, respectively, which were decreased to (15.88±1.04)% and (13.80±0.82)% in combined treatment group, respectively (P<0.05). Combined treatment enhanced the increase in the protein level of cleaved caspase-3 caused by irradiation. The protein levels of p-CDC25C and p-CDK1 were increased in a dose-dependent manner by Tet treatment (P<0.05), while the expression of CDK1 showed no difference among different doses of Tet treatments. The protein levels of p-CDC25C, p-CDK1 and CDK1 showed no difference after the treatment with maximum non-cytotoxic doses of Tet. The combined treatment with irradiation and the maximum non-cytotoxic doses of Tet decreased the protein levels of p-CDC25C and p-CDK1 (P<0.05), increased the expression of cyclin B1, and had no influence on the expression of CDK1 (P<0.05). The combined treatment resulted in an increase in the protein level of p-ERK1 (P<0.05).CONCLUSION: The maximum non-cytotoxic doses of Tet enhance the DNA damage and apoptosis in CNE1 cells and CNE2 cells caused by irradiation, and the mechanism might be associated with ending of G2/M arrest via activation of ERK/CDC25C/CDK1/cyclin B1 pathways.  相似文献   
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ObjectiveTo compare the dose, cardiopulmonary effects and quality of anaesthetic induction in dogs using propofol (10 mg mL–1) and diluted propofol (5 mg mL–1).Study designRandomized, blinded, clinical study.AnimalsA total of 28 client-owned dogs (12 males/16 females).MethodsFollowing intramuscular acepromazine (0.02 mg kg–1) and methadone (0.2 mg kg–1), propofol (UP, 10 mg mL–1) or diluted propofol (DP, 5 mg mL–1) was administered intravenously (0.2 mL kg–1 minute–1) by an anaesthetist unaware of the allocated group to achieve tracheal intubation. Sedation, intubation and induction quality were scored from 0 to 3. Pre- and post-induction pulse rate (PR), respiratory rate (fR) and systolic (SAP), mean (MAP) and diastolic (DAP) arterial blood pressure were compared. Time to first breath and induction dose were recorded. Data were analysed for normality and Mann–Whitney U or Student t tests were performed where appropriate. Significance was set at p < 0.05. Data are presented as mean ± standard deviation or median (range).ResultsThe propofol dose administered to achieve induction was lower in the DP group (2.62 ± 0.48 mg kg–1) than in the UP group (3.48 ± 1.17 mg kg–1) (p = 0.021). No difference was observed in pre- and post-induction PR, SAP, MAP, DAP and fR between groups. The differences between post-induction and pre-induction values of these variables were also similar between groups. Time to first breath did not differ between groups. Sedation scores were similar between groups. Quality of tracheal intubation was marginally better with UP 0 (0–1) than with DP 1 (0–2) (p = 0.036), but overall quality of induction was similar between groups [UP 0 (0–1) and DP 0 (0–1), p = 0.549].Conclusion and clinical relevanceDiluting propofol reduced the dose to induce anaesthesia without significantly altering the cardiopulmonary variables.  相似文献   
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ObjectiveTo describe an approach for ethmoidal nerve block (EBLOCK) and to compare the effects of a maxillary nerve block (MBLOCK), EBLOCK and their combination (M-EBLOCK) on heart rate (HR), systolic (SAP), mean (MAP), diastolic (DAP) arterial pressures and respiratory rate (fR) during nasal stimulation in dogs.Study designProspective, blinded, randomized, crossover placebo-controlled study.AnimalsBeagle dogs (five cadavers, nine live dogs), with a median (interquartile range) weight of 10.5 (10.3–11.0) kg.MethodsThe accuracy of iohexol injections (each 1 mL) at the maxillary and ethmoidal foramina in cadavers was evaluated using computed tomography. Then, anesthetized dogs were administered four bilateral treatments separated by 1 week, saline or 2% lidocaine 1 mL per injection: injections of saline at the maxillary and ethmoidal foramina (Control), injections of lidocaine at the maxillary foramina and saline at the ethmoidal foramina (MBLOCK), injections of saline at the maxillary foramina and lidocaine at the ethmoidal foramina (EBLOCK) and injections of lidocaine at all foramina (M-EBLOCK). The ventral nasal meatus was bilaterally stimulated using cotton swabs, and HR, SAP, MAP, DAP and fR were continuously recorded. Values for each variable were compared before and after stimulation using Wilcoxon signed-rank test. Changes in variables among treatments were analyzed using Mann–Whitney U and Kruskal–Wallis tests (p ≤ 0.05).ResultsComputed tomography revealed iohexol distribution around the openings of the target foramina in all cadavers. In living dogs, HR, SAP, MAP, DAP and fR significantly increased after stimulation within each treatment (p < 0.03). Physiologic responses were significantly attenuated, but not absent, in the M-EBLOCK [HR (p = 0.019), SAP, MAP, DAP and fR (all p ≤ 0.001)] compared with those in the Control.Conclusions and clinical relevanceConcurrent injections of lidocaine at the maxillary and ethmoidal foramina attenuated HR, arterial pressure and fR responses to nasal stimulation in Beagle dogs.  相似文献   
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Canine osteosarcoma is an aggressive cancer, comprising 85% of canine bone neoplasms. Current treatment practices of surgery and chemotherapy increase 1-year survival by only 45%. The curcumin analogue RL71, has demonstrated potent in vitro and in vivo efficacy in several models of human breast cancer through increased apoptosis and cell cycle arrest. Thus, the present study aimed to investigate efficacy of curcumin analogues in two canine osteosarcoma cell lines. Osteosarcoma cell viability was assessed using the sulforhodamine B assay and mechanisms of action were determined by analysing the levels of cell cycle and apoptotic regulatory proteins via Western blotting. Further evidence was obtained using flow cytometry to detect cell cycle distribution and the number of apoptotic cells. RL71 was the most potent curcumin analogue with EC50 values of 0.64 ± 0.04 and 0.38 ± 0.009 μM (n = 3) in D-17 (commercial) and Gracie canine osteosarcoma cells, respectively. RL71 significantly increased the ratio of cleaved-caspase 3 to pro-caspase 3 and the level of apoptotic cells at the 2× and 5× EC50 concentration (p < 0.001, n = 3). Furthermore, at the same concentration, RL71 significantly increased the number of cells in the G2/M phase. In conclusion, RL71 has potent cytotoxic activity in canine osteosarcoma cells triggering G2/M arrest and apoptosis at concentrations achievable in vivo. Future research should further investigate molecular mechanisms for these changes in other canine osteosarcoma cell lines prior to in vivo investigation.  相似文献   
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AIM: The effects of BDM on isolated rat heart in cold cardioplegia were studied. METHODS: Rat heart were subjected to cold cardioplegia at 4℃ for 8, 18 and 24 h.Then each heart was perfused (90 cm H2O) in Langendorff model at 37℃ for 40 min. In the high K+ group(n=24) the hearts were preserved in St.Thomas cardioplegic solution, in BDM group(n=24) hearts were preserved in K-H solution with BDM 30 mmoL/L. RESULTS: After 18 h, heart rate and the coronary flow in BDM group were significantly higher than in high K+ group(P<0.05). Activity of Na+-K+-ATPase in cell membrane and in mitochondrial membrane in the BDM group was significantly higher than high K+ group(P<0.01). After 24 h, all hearts in high K+ group were dead, but were alive in BDM group. CONCLUSION: Under given experiment conditions, BDM did enhance the tolerance to cold ischemia significantly. The results showed that BDM may become a useful agent for prolong the storage period of heart in cold cardioglegia.  相似文献   
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Equine anaesthesia is associated with a high risk of perioperative morbidity and mortality, particularly in the recovery period. Cardiovascular collapse and cardiopulmonary arrest (CPA) have been reported to account for one-third of anaesthesia-related perioperative deaths in the horse. This case report describes the successful cardiopulmonary resuscitation of a healthy adult Thoroughbred mare that developed cardiovascular collapse and subsequent CPA following positioning in the recovery box after general anaesthesia in the Trendelenburg position. Cardiopulmonary resuscitation (CPR) was instigated and included thoracic compressions, intermittent positive pressure ventilation and adrenaline administered via the intravenous and intra-tracheal routes. Return of spontaneous circulation (ROSC) was detected 5 min and 50 s after the start of CPR. A stable stance was achieved approximately 100 min after ROSC. The mare was discharged from the hospital 3 days later with no known complications. To the authors’ knowledge, this is the first case report documenting CPA following general anaesthesia in the Trendelenburg position in a horse, with subsequent successful CPR. The precise cause of the CPA is unknown but a number of plausible hypothesis are discussed including hypoventilation and a Bezold-Jarisch reflex.  相似文献   
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Objective To determine the electrocardiographic and cardiopulmonary effects of romifidine with and without prior or concurrent administration of glycopyrrolate. Study design Randomized crossover experimental study. Animals Six (three male, three female) cross‐bred dogs weighing 23 ± 2.4 kg. Methods Baseline cardiopulmonary measurements were obtained in conscious dogs and one of five treatments was administered. Glycopyrrolate (G) 0.01 mg kg?1, or saline (S) 0.5 mL, were administered IM as premedication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40 µg kg?1; T2, Gp + RO (40 µg kg?1); T3, Sp + RO 120 µg kg?1; T4, Gp + RO (120 µg kg?1); T5, Sp + Gc + RO (120 µg kg?1). Romifidine or RO + Gc was administered subcutaneously 20 minutes after premedication (time 0), and further measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main treatment effect was evaluated using two‐way anova for repeated measures, followed by one‐way anova and a post‐hoc least squares difference test with a modified Bonferroni correction (p < 0.02). A Student's t‐test was used to compare the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05). Results Both low‐ and high‐dose RO (T1, T3) significantly decreased heart rate (HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and increased arterial blood pressure (SAP), systemic vascular resistance (SVR), pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High‐dose RO produced greater increases in SVR and SAP measurements. Neither dose of RO produced an alteration in blood gas values or the alveolar to arterial oxygen gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes between T1/T2 and T3/T4. Increases in SAP were dose related with significant differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were highest in animals receiving Gp or Gc. High‐dose RO groups (T3, T4) had higher values for SVR than low‐dose RO groups (T1, T2), unrelated to G administration. There was an increase in PAOP in all treatments. The oxygen extraction ratio was increased with all treatments: larger increases were observed in T1, T3 and T4 compared with only minimal changes in T2. Concurrent G administration was associated with an increased frequency of high‐grade second‐degree atrioventricular heart block with variable conduction at 10 and 20 minutes. Conclusions Romifidine produced effects consistent with other selective α2‐adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially offset the decrease in CI associated with RO administration. Glycopyrrolate premedication produced an initial tachycardia and added to the increase in SAP associated with RO. Concurrent G administration was associated with a higher frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO sedation did not alter blood gas values. Clinical relevance It appears likely that G administration prior to or concurrent with RO produces an increase in myocardial workload and oxygen demand suggesting that this combination should not be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen extraction ratio with T2 suggests that G may be beneficial with lower doses of RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is not advised.  相似文献   
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