ABSTRACT
Objective To investigate the role of erlotinib in the expression of surfactant protein A (SP-A) in LPS-induced acute lung injury (ALI) of mice model.Methods C57BL/6 mice were randomly (random number)divided into control group (n=6),ER group (n=6),LPS group (n=6),and ER+LPS group (n=6).In the LPS group,2 mg/kg LPS was instilled into trachea of mice to induce lung injury.In control group,normal saline was instilled into trachea of mice instead.In the ER+LPS group and ER group,100 mg/kg of edotinib was instilled into stomach of mice,and one hour later.2 mg/kg LPS was instilled into trachea of mice in ER+PLS group to induce lung injury.Twenty-four hours later,bronchoalveolar lavage fluid (BALF) and lung tissue of mice in four groups were collected.HE staining were used for evaluating pathological changes of lung injury.Lung wet/dry weight ratio,protein concentrations and total cell numbers in the BALF were measured to determine the degree of pulmonary edema.Immunohistochemical staining and Western Blot were used for testing the protein expression of SP-A,Data of multiple groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by the least significant difference (LSD) tests.Results There was no significant difference in lung injury score (LIS) between control group (0.056±0.008) and ER (0.064±0.037) group,The LIS in LPS group (0.846-±0.047) was higher than that in control group,however the LIS in ER+LPS group (0.279±0.020) was significant lower than that in LPS group (P ＜ 0.05).Lung wet/dry weight,SP-A concentration and total cell numbers in the bronchoalveolar lavage fluid revealed that the degree of pulmonary edema in LPS group was higher than that in control group,and this pulmonary edema was reversed by erlotinib treatment.Immunohistochemical staining and Western blot showed that the expression of SP-A in LPS group was decreased compared with control group,but it was recovered after erlotinib treatment (P ＜ 0.05).Conclusions Erlotinib could protect the LPS-induced ALI,and it may be related to the regulation of SP-A.
ABSTRACT
Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells (denoted as I ( che )) was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.
Subject(s)
Anesthetics, Inhalation , Biological Assay , Methods , Cell Movement , Physiology , Chemotaxis , Physiology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Methods , Paramecium tetraurelia , Physiology , Volatile Organic CompoundsABSTRACT
Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells (denoted as I ( che )) was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.
ABSTRACT
Cognitive decline is a common complication after cardiac surgery with cardiopulmonary bypass (CPB), but as such no pharmacological therapy has been shown to be efficacious in preventing the decline. However, gastrodin has been shown to have multi-pharmacological effects on neurological functions. We undertook this study to test the hypothesis that gastrodin would potentially prevent CPB-associated neurocognitive decline. We randomly assigned 200 patients undergoing mitral valve replacement surgery to receive either gastrodin (40 mg/kg) or saline after the induction of anesthesia and subsequently evaluated cognitive function before surgery, at discharge, and at 3rd month after surgery by using a battery of five neurocognitive tests, or adverse effects of gastrodin postoperatively. Neurocognitive decline in postoperative function was defined as a drop of 1 SD or more in the scores on tests of any one of the four domains of cognitive function. Cognitive decline occurred in 9% of the patients in the gastrodin group in contrast to 42% in the control group (P<0.01) at discharge. Cognitive outcome could be determined at 3rd month in 87 patients in the gastrodin group and 89 in the control group. Cognitive decline was detected in 6% in the gastrodin group and 31% in the control group (P<0.01). The incidences of possible adverse effects were similar between two groups. These results indicate that gastrodin is an effective and a safe drug for the prevention of neurocognitive decline in patients undergoing mitral valve replacement surgery with CPB.
ABSTRACT
Objective To explore a safe and efficient method for endotracheal intubation in mice.Methods 60 BALB/c mice were random divided into 2 groups, direct intubation under direct vision group, ( n = 30) and direct intubation under light by transillumination group ( n = 30).After successful tracheal intubation at the first judgment, mouse received a tracheal instillation of 3 mg/kg lipopolysaccharide.Bronchoalveolar lavage (BAL) was then performed three times with 0.8 ml sterile saline.Exudate cells were centrifuged and stained with Wright's fluid.Whether the intubation indeed succeeded was judged by the amount of neutrophil infiltrated into the lungs.The mortality after intubation, the time consumed for each successful tracheal intubation and the times of attempting for intubation in two groups were assessed to approve the efficiency of two techniques.Results Eight vs.two mice died within 24 hours in two groups respectively.The time consumed for each successful tracheal intubation and success rate for the first time for two groups were (92.6 ±23.4)s vs (64.0±20.1)s and 53.3% vs 86.7% respectively, which the consumed time was significantly different, while the final success rate almost the same for the two groups.Conclusion Both direct intubation under direct vision and intubation under light by transillumination can successfully intubate the tube into the trachea.But direct intubation under direct vision by transillumination is more efficient and safe in endotracheal intubation in mice.