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@#Objective: To investigate the relationship between drug resistance and expression of ABC-binding cassette subfamily B member 1 (ABCB1) as well as its promoter methylation in pancreatic cancer. Methods: Fifteen pairs of pancreatic cancerous tissues and corresponding para-cancerous tissues, which were pathologically verified in Fujian Cancer Hospital from August 2015 to August 2018, were collected for this study; in addition, 3 cases of normal pancreatic tissues and pancreatic cancer cell line SW1990 were also collected. Gemcitabine (GEM)-resistant human pancreatic cancer cell line SW1990/GZ was induced by intermittent concentration gradient multiplication method. The expression level ofABCB1 in SW1990 cells, SW1990/GZ cells, pancreatic cancer tissues and apara-cancerous tissues was detected by qPCR. Methylation of ABCB1 promoter region in SW1990 cells, SW1990/GZ cells and pancreatic cancerous tissues was determined by MSP-PCR. Results: Compared with SW1990 cells, the morphology of SW1990/GZ cells showed more vacuoles, more mitotic images, clumpy growth and increased drug resistance (P<0.05). ABCB1 expression in pancreatic cancer tissues was significantly higher than that in para-cancerous tissues (P<0.01). The expression of ABCB1 in SW1990 and SW1990/GZ cells was significantly higher than that in normal pancreatic tissues (P<0.05 or P<0.01), and the expression of ABCB1 in SW1990/GZ cells was higher than that in SW1990 cells (P<0.05). ABCB1 promoters in SW1990, SW1990/GZ cells and normal pancreatic tissues were hypomethylated. Rate of methylation in pancreatic can cerous tissues and normalpancreatic tissues was 6.7%(1/15) and 0.00%(0/3) respectively,and the difference was statistically insignificant (all P>0.05). Conclusion: Increased ABCB1 expression in pancreatic cancer tissues and cells is associated with drug resistance, but its gene expression does not depend on promoter methylation regulation.
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Objective To establish an HPLC method for the determination of anti-influenza drug GZ830 and its related substances, and investigate the degradation of GZ830. Methods The degradation of GZ830 under the conditions with different pH and temperatures was investigated with HPLC method to explore the degradation principle. Results The HPLC method for the determination of GZ830 was established. The linear relationship between the drug and the peak area was good in the concentration range of 160-1200 μg/ml (r=0.9998). GZ830 was easily degraded under alkaline conditions and could not tolerate high temperatures. The degradation of GZ80 did not occur when its aqueous solution was kept at 40℃ for 6 h. However, after heating at 80℃ for 6 h, about 2.4％GZ80 was degraded and the degradation rate reached about 7％ after kept at 115℃ for 30 min. Conclusion Under the optimized chromatographic conditions, GZ830 was well separated from the degraded products, and the HPLC method possessed high sensitivity and good specificity for the determination of GZ80, and the degradation of GZ80 was different under different conditions.
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Objective To study the physical-chemical parameters of antiviral drug GZ 914 and provide data for the preparation design .Methods The appearance , crystal structure and solubility of GZ 914 were investigated .An HPLC method was established to determine the content of GZ 914 in vitro before oil/water partition coefficient and solubility in different pH experiments were calculated .Results GZ914 was a straw yellow powder with a crystalline structure , low water-solubility and good lipotropy .The HPLC method had a good linear relationship within the range of 12-60 μg/ml (r=0.9998).The oil/water partition coefficient of GZ914 was 1.9.Conclusion This analytical method is accurate and reliable.The oil/water partition coefficient indicates that the drug could be formulated as an oral solid preparation.
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Objective:To investigate effects of depside salt from salvia miltiorrhiza(DSSM)on the dental pulp of rats under repeated exposure to +Gz acceleration.Methods:27 male SD rats were randomly divided into 9 groups(n =3).The rats in negative control group was only fixed with rats kept-keeling device,in positive control group were exposed to +5 Gz and +10 Gz respectively for 30 s each time,5 times per day,4 days per week,for 3 consecutive weeks.The rats in other groups were respectively given DSSMat 2,6 and 18 mg/kg respectively 30 min before each +Gz exposure.The rats in negative and positive control groups were injected with 0.9%sodium chloride solution 30 min prior to +Gz exposure.After the experiment,The pulp changes were observed by HE staining.Real time qPCR was applied to determine the relative expression of heat sheck protein(HSP70)mRNA.Results:+Gz exposure decreased the activity degree of the rats,and resulted in damage of rat dental pulp.With the increase of +Gz value,the relative expression of HSP70 mRNA was increased(P ＜0.05).HSP70 mRNA expression in drug groups was less than that in their own positive control groups,but showed statistical significance only in the 18 mg/kg and +10 Gz group(P ＜0.05).Conclusion:+Gz exposure may dam-age dental pulp.DSSMhas certain protective effect under +Gz exposure.
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Objective To study the effect of rhodiola crenulata compound on serum corticosterone and myocardial glucocorticoid receptor ( GR) in rats exposed high sustained +Gz.Methods Seventy-two healthy SD rats were randomly divided into six groups: blank control group, stress control group, +10 Gz stress group and low, medium, high dose drug group, with twelve rats in each.20 mL/kg menstruum was fed to each rat once per day for 14 days.Low, medium and high dose drug group were fed with rhodiola crenulata compound at doses of 0.75 g/kg, 1.5 g/kg and 3.0 g/kg respectively, the other three groups were fed with equal volume saline.Rats were exposed to high +Gz in 15th day.The concentration of corticosterone in the serum of each group rats was detected with ELISA. Western blot was used to detect the expressions of GR in the myocardium of each group rats .Results The content of corticosterone was significantly elevated in +10Gz stress group, while the expression of GR in the myocardium was markedly declined (P <0.01,P <0.05).However, compound preconditioning could decrease concentration of corticosterone in the serum and enhance the expression of GR in the myocardium from rats after +10 Gz exposure. The corticosterone concentration of medium and high dose drug groups was significantly lower and the level of GR expression in the myocardium was significantly higher than that of +10 Gz stress group ( P <0.05 , P <0.01 ) . Conclusion Rhodiola crenulata compound preconditioning could regulate the concentration of corticosterone in the serum and the level of GR expression in the myocardium of the rats exposed +10 Gz, which may be related with its protective effect on high sustained +Gz-induced injury of myocardium.
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Objective To observe changes of expression level of HSP70 protein in rat hippocampus after exposure to +Gz of different magnitudes and to investigate the machanism of HSP70 protein induced by +Gz exposure.Method One hundred rats were divided into: control group,+2 Gz group,+6 Gz group and +10 Gz group.The experimental rats were exposed to +2 Gz,+6 Gz and +10 Gz for 3 min respectively.The rats were killed 6 h,1 d,2 d,4 d,6 d after exposure and brain specimens were made for examination under microscope.The changes of HSP70 protein expression level were determined with immunohistochemical technology.Result The HSP70 protein expression level in the 3 experimental groups were significantly higher than that in control group.It began to rise 6 h after exposure,reached the peak after 1 d,and resumed to normal 6 d after exposure.The expression level was the highest in +6 Gz group and the lowest in +10 Gz group.Conclusion +Gz exposure can induce obvious changes of HSP70 protein expression level and the most prominent changes are found in rats after exposure to +6 Gz group.
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Objective To investigate changes of learning ability and somatostatin (SS) changes after positive acceleration (+Gz) exposures. Mehtod Eighty male SD rats were randomly divided into 3groups: control group(Con), +6 Gz/3 min group ( +6 Gz), and +10 Gz/3 min group ( +10 Gz),8 rats in each group. Changes of learning ability in rats were observed at 0 d, 2 d, 4 d and 6 d after + Gz exposure. SS in hippocampus was measured by RIA at 0 d, 2 d and 4 d after + Gz exposures ( there were 8 rats every time, in each group). Result In Y-maze test,number of correct response decreased significantly (P ＜0.01 ), and total reaction time increased significantly(P ＜0.01 ) in +6Gz and +10 Gz groups as compared with control group; number of correct response and total reaction time in +10 Gz group changed significantly at 0 d(P ＜0.01 or P ＜0.05) as compared with +6Gz group. RIA showed that, content of SS in hippocampus declined at 0 d and 2 d(P ＜0.05 or P ＜0.01) in +6 Gz and + 10 Gz groups as compared with control group. Conclusion + Gz exposure could impair learning ability of rats, and inhibit expression of SS in hippocampus.
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Objective To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure.Method Mice were arranged into control group (group A),+Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C).Each group contains 12 mice.Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min +10 Gz.Distilled water was gavaged to group B mice 3 h before +Gz exposure.On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice.Water Maze test was done and scores were recorded in all groups.After the Water Maze test was completed,blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and γ-glutamyl transferase (GGT) activity evaluation. Result After +Gz exposure,longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine(DA) was significantly reduced in group C as compared with group B.Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. Conclusion High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes).It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group,which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.
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BACKGROUND AND METHOD: For decades, the presence of aortic insufficiency (AI) has been considered a potential hazard in military aviation and has generally excluded aircrew from high performance flight. The cardiovascular effect of repeated exposure of high +Gz forces associated with AI is largely unknown. To evaluate whether the flying of High Performance Aircraft (HPA) was detrimental to subjects with AI, we performed a retrospective review. we studied 32 asymptomatic patients in whom 16 of them had flying time with AI in HPA(Group I), others(GroupII, Control Gr.) in Low-G Aircraft(LGA). Among them, the data of 24 patients were available, 12 in group I., and 12 in group II. The two groups were matched for age, severity of AI, and flying time. RESULTS: Interval echocardiographic, and cineangiographic studies were obtained over a mean period of 4.6+/-2.6 years in group I and 5.9+/-4.2 years in group II (range, 0.9 to 12.7 years) and mean flying time with AI of 528.1+/-435.0 hours in group I and 865.0+/-816.1 hours in group II (range, 50 to 2290 hours). By paired-t test, there were no significant differences between both groups in left ventricular end-diastolic dimension (LVEDD), end-systolic dimension (LVESD), aortic dimension (Ao.D) and fractional shortening (FS) by echocardiography (p>0.05) and by multiple linear regression, there were no significant interval changes of above values in Gr. I according to increasing of flying time with AI (p>0.05). Visual grade by doppler echocardiography or aortic cineangiography increased 1 patient in Gr.I and 2 patients in Gr.II within no more than one grade. CONCLUSION: Thus, this study demonstrated that : 1) Quantitative echocardiographic measurements such as LEVDD, LVESD, Ao.D and FS didn't show significant interval change in Gr.I.2) A single subject with a minor increase in AI severity together with no difference between the HPA and LPA groups argue for a relatively chronic effect of high G exposure in aircrew with mild AI.
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Humans , Aircraft , Aviation , Cineangiography , Diptera , Echocardiography , Echocardiography, Doppler , Linear Models , Military Personnel , Retrospective StudiesABSTRACT
BACKGROUND: Fighter pilots are frequently exposed to high gravitational acceleration force acting along the body axis from the head to the feet (+GZ) and this gravitational force causes considerable strain on several organ systems, including cardiovascular system and kidneys. Proteinuria had been observed after +GZ stress but the characteristics of urinary protein and the mechanism of proteinuria are not closely investigated up to now. METHODS: A total of 44 student pilots were exposed to +6GZ for 30 seconds using Human Centrifuge and urine samples were collected before and after +GZ load. The amount of urinary protein was measured quantitatively and semiquantitatively with chemistry and dipstick, and the protein components were analysed with electrophoresis. RESULTS: After a total of 44 student pilots were exposed to +6GZ for 30 seconds without anti-G suit, 19 urine samples were positive in dipstick protein test and electrophoresis revealed that their major protein component was albumin. The amount of urinary protein excretion and urinary protein and creatinine ratios (UProt/UCr) were significantly increased to levels of 33.4+/-29.3 mg/dL and 0.239+/-0.203 in comparison with pre-G training levels of 8.8+/-4.3 mg/dL and 0.046+/-0.018, respectively. All 44 urine samples collected the next day of G training were negative in dipstick protein test and had protein levels of 6.8+/-3.0 mg/dL. Of 19 subjects showed proteinuria, 15 performed the same +GZ training again with anti-G suit and so only three urine samples were positive in dip stick protein test. CONCLUSIONS: These results indicates that transient proteinuria can be developed after high +GZ stress most possibly due to increased glomerular permeability of albumin and be effectively protected by the anti-G suit.
Subject(s)
Humans , Acceleration , Axis, Cervical Vertebra , Cardiovascular System , Chemistry , Creatinine , Electrophoresis , Foot , Head , Kidney , Permeability , ProteinuriaABSTRACT
Centrifuge high +Gz training has been reported to provoke cardiac arrhythmias in ostensibly healthy individuals, and ECG monitoring of aircrew undergoing such training is recommended for their safety. However, there are few reports about ECG responses during actual high +Gz flight. Therefore, we start this study to determine the ECG responses during actual high +Gzz flight of F-5. In our study, twenty-four pilots, ages 25-37 and one Flight Surgeon were monitored by Holter ECG monitor for four hours, which included periods before, during, and after either a high +Gz or low +Gz flight in a F-5, Actual flight times ranged from 28-78 minutes. Sixteen(16) pilots were monitored in both high +Gz (>5Gz) and low +Gz (<3Gz) flight, the flight surgeon and seven(7) pilots were monitored only in high +Gz flight, one pilot was monitored only in low +Gz flight. Heart rate(HR) and cardiac rhythm were evaluated during a total of 41 flights. During the high +Gz flight, there was one episode of visual black out and dyspnea, three episodes of gray out, and one episode of fatigue. During the low +Gz flight, there were two episodes of coughing. The frequency of occurrence of Ventricular Ectopic Beats (VEs) (Premature Ventricular Contractions (PVCs), especially in-flight VEs(PVCs), was significantly higher in pilots who hart symptoms during the flight as compared to pilots who had no symptoms in one pilot, we recorded 16 VEs (PVCs) over the four houris wlth 10 VEs occurring during the flight. Another pilot experienced 254 Supraventricular ectopic beats (SVEs)(Premature Atrial Contractions (PVCs) or Premature Junctional Contractions (PVCs)) with a total of 87 SVEs recorded during the flight. In high +Gz flight, there were, overall, twelve (12) cases of VEs and fifteen (15) cases of SVEs. In low +Gz flight, there were four (4) cases of VEs anti ten (10) cases of SVEs. In addition, We correlated the HR 30 minutes before flight (range of 52-117 bpm) with maximum in-flight HR (range of 92-178 bpm). We found that the maximum HR during the flight was lower with increased pilot's experience (i.e., age and total flight time). There was no significant difference noted in HR and cardiac arrhythmias when comparing high +Gz and low +Gz flight. During the high +Gz flight, stress may cause symptoms with minor cardiac arrhythmias. Further studies shou1d be done to better correlate the exact relationship and timing between onset of +Gz forces, arrhythmias, and occurrence of adverse clinical symptoms.
Subject(s)
Arrhythmias, Cardiac , Cough , Dyspnea , Electrocardiography , Fatigue , Heart , Ventricular Premature ComplexesABSTRACT
The purpose of this study is to observe the changes in gene expressions of bcl 2, bax, p53 and interleukin 1? converting enzyme (ICE) in the cerebral tissue of rat exposed to repeated +Gz, and to explore the pathogenetic role of apoptosis in brain damage induced by repeated +Gz exposures. The expression levels of bcl 2, bax, p53 and ICE in cerebral tissue of rats exposed to repeated +Gz were measured by semi quantitative reverse transcription polymerase chain reaction (RT PCR), and the apoptotic cells in brain tissue were detected by terminal deoxynuleotidyl transferase mediated dUTP nick end labeling technique. The results showed that the bcl 2 expression levels in the brain 6h and 24h after repeated +Gz exposures were significantly lower than those of control group, whereas the bax, p53 and ICE expression levels in the brains tissue 6h and 24h after repeated +Gz exposures were significantly higher than those of control group. Apoptotic cells could be observed in cerebral cortex, CA1 subregion of hippocampus and striatum at 6h and 24h after repeated +Gz exposures. It is suggested that the changes in bcl 2, bax, p53 and ICE expressions in rat brain can be induced by repeated +Gz exposures and apoptosis might be one of the molecular mechanisms of brain damage induced by repeated +Gz exposures