BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simu...BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simulated weightlessness, and the relationship between pretreatment and injection of succinylcholine has not been determined yet. OBJECTIVE ： To investigate the changes of expression of Fos in PAG induced by injured electrostimulation pretreatment and injection of succinylcholine at 2 weeks after simulated weightlessness.DESIGN： Observational and controlled animal study.SETTING： Department of Physiology, Medical School, Xi＇an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education. MATERIALS： A total of 24 adult female SD rats, of clean grade and weighing 180-220 g, were selected in this study. METHODS： The experiment was completed in the Experimental Animal Center of Xi＇an Jiaotong University.① All rats were randomly divided into 2 groups according to body mass： simulated weightlessness group and control group with 12 in each group. And then, each group was also divided into 3 subgroups： electrostimulation group, succinylcholine-pretreatment group and succinylcholine-injection group with 4 in each subgroup. ②The model of weightlessness was simulated by tail-suspended female rats, which were described and modified by Cheng Jie. Rats in normal control group were given the same interventions as simulated weightlessness group except for tail-suspended. ③ Experimental method： The rats in electrostimulation group were given nociceptive stimulus by a pair of subcutaneous electrodes inserted into 1 and 5 claw of left hindlimb. The stimulus （current： 10 mA; duration： 1 ms; interval： 1 s） lasted for 30 minutes. The rats in succinylcholine-pretreatment group received stimulus after intravenous administration of succinylcholine, rats in succinylcholine-injection group were not given stimulus, just received succinylcholine. ④ All rats were perfused and fixed after 2 hours from the end of stimulation. The brains were removed, and serial frozen sections of midbrain were stained using immunocytochemical method, observed and taken photos under light-microscope. The number and morphological characters of Fos-immunoreactive （Fos-IR） neurons in ventrolateral part of PAG were investigated. MAIN OUTCOME MEASURES： The alterations in number and morphological characters of Fos-IR neurons in ventrolateral PAG of all rats.RESULTS： A total of 24 rats were involved in the final analysis. ① The morphological changes of Fos-IR neurons： The expressions of Fos in ventrolateral part of PAG were observed in both control and simulated weightlessness groups rats after being given nociceptive stimulus. As compared with control group, Fos-IR neurons in simulated weightlessness group were dyed lightly, cellular integrity was impaired, and cellular verge was unclear. ② The numbers of Fos-IR neurons： In control group, the numbers of Fos-IR neurons in ventrolateral part of PAG in simulated weightlessness group were obviously lower than succinylcholine-pretreatment group, but obviously higher than succinylcholine-injection group （46.94±3.38, 71.06±8.96 and 35.04±4.62, respectively, P 〈 0.05）. In 14-day simulated weightlessness group, the numbers of Fos-IR neurons in electrostimulation group were also obviously lower than succinylcholine-pretreatment group, and obviously higher than succinylcholine-injection group （27.77±3.27, 32.91±2.99 and 11.75±1.00, respectively, P 〈 0.05）. The numbers of Fos-IR neurons in all subgroups in control group were obviously higher than those subgroups in simulated weightlessness group. Compared with electrostimulation group, the percentage of expression of Fos in ventrolateral part of PAG responsed to nociceptive stimulus after administration of succinylcholine （SCH） was increased to 51.83% in control group and 18.51% in simulated weightlessness group.CONCLUSION ：① The expression of Fos in neurons in ventrolateral part of PAG were increased by the pretreatment of SCH before nociceptive stimulus.② Nociceptive stimulus could increase the expression of Fos in neurons in ventrolateral part of PAG. ③ The numbers of Fos-IR neurons in ventrolateral part of PAG were decreased obviously after 2-week simulated weightlessness.展开更多
Objective To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastric and colorectal adenocarcinoma (GCRA) Past studies h...Objective To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastric and colorectal adenocarcinoma (GCRA) Past studies have attributed the antitumor effect of cimetidine to its immunomodulatory property, which led to an increase of cellular immunity Whether there are other possible mechanisms by which cimetidine exerts its antitumor function is unknown 49 patients with GCRA were randomized into treatment group (n=25) and control group (n=24) based on whether cimetidine was applied to them during the perioperative periold The treatment group started oral cimetidine intake 400mg, tid, 7-10d before oiperation, followed by curative surgery 'The control group did not receive cimetidine Tumor specimens were paraffin embedded for 4μm thick microsection and stained with (1) hematoxylin and eosin (HE) for the morphometric measurements of tumor cell nuclear area (NA), nuclear perimeter (NP), maximal nuclear diameter (MMND) and minimal nuclea4r diameter (MNND); (2) feulgen stain for tumor nuclear DNA content analysis by IBAS Image Analyzer The percentages (%) of diploidy (2C), tripletetraploidy (3C 4C), quintuple ploidy (5C) and >quintuple ploidy (>5C) tumor cells were calculated, using the mean value of DNA content of 50 lymphocytes as normal 2C control 3C 5C cells were designated as law aneuploid cells and >5C cells as high aneupoid cells Results The clinicopathological variables between the two groups were balanced and comparable There were no statistically significant differences between bthe treatment and control groups in regard of the following parameters: age, gender, tumor location, pathological type, TNM stage, and degree of differentiation The NA (μm 2), NP (μm), MMND (μm) and MNND (μm) for treatm ent group/control group were 23 54±5 08/34 698±10 18 ( P <0 001), 22 06±4 43/24 88±4 05 ( P <0 05),7 84±1 64/8 62±1 24 ( P >0 05), and 4 42±0 61/5 41±0 89 ( P <0 001), respectively The percentages (%) of 2C, 3C 4C, 5C and >5C tumor cells for treatment group/control group were 16 64±2 58/5 35±2 14 ( P <0 002), 39 84±2 28/35 70±3 58 ( P >0 50), 12 42±5 00/14 48±0 74 ( P >0 20), 31 11±6 86/45 97±3 82 ( P <0 005), respectively In the treatment group, there was a tendency tiowards low aneuploid tumor cells from high an euploid tumor cells However, high aneuploid tumor cells predominated in the control group Conclusion Perioperative administration of cimetidine to GCRA patients could decrease the size of tumor cell nuclei, raise the percentage of diploid tumor cells, and partially convery high aneuploid tumor cells into low aneuploid tumor cells All of these effects may in turn help reduce the proliferative potential and invasiveness of tumor cells The direct inhibitory functions on tumor cell nuclei may be a new antitumor mechanism of cimetidine, in addition to its immunomodulatory action展开更多
基金the National Natural Science Foundation of China, No. 30300106
文摘BACKGROUND： Expression of Fos in neurons of periaqueductal gray （PAG） is used to reflect the excitability. However, changes of expression of Fos in neurons of PAG are caused by injured electrostimulation after simulated weightlessness, and the relationship between pretreatment and injection of succinylcholine has not been determined yet. OBJECTIVE ： To investigate the changes of expression of Fos in PAG induced by injured electrostimulation pretreatment and injection of succinylcholine at 2 weeks after simulated weightlessness.DESIGN： Observational and controlled animal study.SETTING： Department of Physiology, Medical School, Xi＇an Jiaotong University; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education. MATERIALS： A total of 24 adult female SD rats, of clean grade and weighing 180-220 g, were selected in this study. METHODS： The experiment was completed in the Experimental Animal Center of Xi＇an Jiaotong University.① All rats were randomly divided into 2 groups according to body mass： simulated weightlessness group and control group with 12 in each group. And then, each group was also divided into 3 subgroups： electrostimulation group, succinylcholine-pretreatment group and succinylcholine-injection group with 4 in each subgroup. ②The model of weightlessness was simulated by tail-suspended female rats, which were described and modified by Cheng Jie. Rats in normal control group were given the same interventions as simulated weightlessness group except for tail-suspended. ③ Experimental method： The rats in electrostimulation group were given nociceptive stimulus by a pair of subcutaneous electrodes inserted into 1 and 5 claw of left hindlimb. The stimulus （current： 10 mA; duration： 1 ms; interval： 1 s） lasted for 30 minutes. The rats in succinylcholine-pretreatment group received stimulus after intravenous administration of succinylcholine, rats in succinylcholine-injection group were not given stimulus, just received succinylcholine. ④ All rats were perfused and fixed after 2 hours from the end of stimulation. The brains were removed, and serial frozen sections of midbrain were stained using immunocytochemical method, observed and taken photos under light-microscope. The number and morphological characters of Fos-immunoreactive （Fos-IR） neurons in ventrolateral part of PAG were investigated. MAIN OUTCOME MEASURES： The alterations in number and morphological characters of Fos-IR neurons in ventrolateral PAG of all rats.RESULTS： A total of 24 rats were involved in the final analysis. ① The morphological changes of Fos-IR neurons： The expressions of Fos in ventrolateral part of PAG were observed in both control and simulated weightlessness groups rats after being given nociceptive stimulus. As compared with control group, Fos-IR neurons in simulated weightlessness group were dyed lightly, cellular integrity was impaired, and cellular verge was unclear. ② The numbers of Fos-IR neurons： In control group, the numbers of Fos-IR neurons in ventrolateral part of PAG in simulated weightlessness group were obviously lower than succinylcholine-pretreatment group, but obviously higher than succinylcholine-injection group （46.94±3.38, 71.06±8.96 and 35.04±4.62, respectively, P 〈 0.05）. In 14-day simulated weightlessness group, the numbers of Fos-IR neurons in electrostimulation group were also obviously lower than succinylcholine-pretreatment group, and obviously higher than succinylcholine-injection group （27.77±3.27, 32.91±2.99 and 11.75±1.00, respectively, P 〈 0.05）. The numbers of Fos-IR neurons in all subgroups in control group were obviously higher than those subgroups in simulated weightlessness group. Compared with electrostimulation group, the percentage of expression of Fos in ventrolateral part of PAG responsed to nociceptive stimulus after administration of succinylcholine （SCH） was increased to 51.83% in control group and 18.51% in simulated weightlessness group.CONCLUSION ：① The expression of Fos in neurons in ventrolateral part of PAG were increased by the pretreatment of SCH before nociceptive stimulus.② Nociceptive stimulus could increase the expression of Fos in neurons in ventrolateral part of PAG. ③ The numbers of Fos-IR neurons in ventrolateral part of PAG were decreased obviously after 2-week simulated weightlessness.
文摘Objective To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastric and colorectal adenocarcinoma (GCRA) Past studies have attributed the antitumor effect of cimetidine to its immunomodulatory property, which led to an increase of cellular immunity Whether there are other possible mechanisms by which cimetidine exerts its antitumor function is unknown 49 patients with GCRA were randomized into treatment group (n=25) and control group (n=24) based on whether cimetidine was applied to them during the perioperative periold The treatment group started oral cimetidine intake 400mg, tid, 7-10d before oiperation, followed by curative surgery 'The control group did not receive cimetidine Tumor specimens were paraffin embedded for 4μm thick microsection and stained with (1) hematoxylin and eosin (HE) for the morphometric measurements of tumor cell nuclear area (NA), nuclear perimeter (NP), maximal nuclear diameter (MMND) and minimal nuclea4r diameter (MNND); (2) feulgen stain for tumor nuclear DNA content analysis by IBAS Image Analyzer The percentages (%) of diploidy (2C), tripletetraploidy (3C 4C), quintuple ploidy (5C) and >quintuple ploidy (>5C) tumor cells were calculated, using the mean value of DNA content of 50 lymphocytes as normal 2C control 3C 5C cells were designated as law aneuploid cells and >5C cells as high aneupoid cells Results The clinicopathological variables between the two groups were balanced and comparable There were no statistically significant differences between bthe treatment and control groups in regard of the following parameters: age, gender, tumor location, pathological type, TNM stage, and degree of differentiation The NA (μm 2), NP (μm), MMND (μm) and MNND (μm) for treatm ent group/control group were 23 54±5 08/34 698±10 18 ( P <0 001), 22 06±4 43/24 88±4 05 ( P <0 05),7 84±1 64/8 62±1 24 ( P >0 05), and 4 42±0 61/5 41±0 89 ( P <0 001), respectively The percentages (%) of 2C, 3C 4C, 5C and >5C tumor cells for treatment group/control group were 16 64±2 58/5 35±2 14 ( P <0 002), 39 84±2 28/35 70±3 58 ( P >0 50), 12 42±5 00/14 48±0 74 ( P >0 20), 31 11±6 86/45 97±3 82 ( P <0 005), respectively In the treatment group, there was a tendency tiowards low aneuploid tumor cells from high an euploid tumor cells However, high aneuploid tumor cells predominated in the control group Conclusion Perioperative administration of cimetidine to GCRA patients could decrease the size of tumor cell nuclei, raise the percentage of diploid tumor cells, and partially convery high aneuploid tumor cells into low aneuploid tumor cells All of these effects may in turn help reduce the proliferative potential and invasiveness of tumor cells The direct inhibitory functions on tumor cell nuclei may be a new antitumor mechanism of cimetidine, in addition to its immunomodulatory action
