The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy ar...The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation(GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity.展开更多
Objective.The present study investigated the role of endogenous carbon monoxide(CO)in the pathogenesis of neointimal formation induced by balloon injury in rat. Method.Endothelial denudation ...Objective.The present study investigated the role of endogenous carbon monoxide(CO)in the pathogenesis of neointimal formation induced by balloon injury in rat. Method.Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter.DNA,collagen and elastin contents of each intima media were estimated;and heme oxygenase(HO)activity and CO production in vascular smooth muscle cell(VSMC)were measured after administration of HO inhibitor. Result.Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury,and at the same time HO activity and CO production in VSMC were markedly increased Administration of HO inhibitor,zinc deuteroporphyrin 2,4 bisglycol(ZnDPBG),could effectively inhibit HO activity and CO production,significantly enhance neointimal formation(aortic intima/media ratio were 21 4±1 8% vs 17 6±2 0%,P<0 05 on day 7;and 30 5±2 4% vs 23 0±2 2%,P<0 01 on day 21,respectively,compared with balloon alone group). Conclusion.We concluded that 1)inhibition of CO production may enhance neointimal formation induced by endothelial denudation,implying endogenous CO play an protective role in response to vascular injury,and 2)induction of HO activity may be applied clinically for preventing restenosis after angioplasty.展开更多
Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with rela...Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.展开更多
This paper reports that lesions of the medial frontal cortex (MFC) caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766, an analog of ACTH- (4-9). Wis...This paper reports that lesions of the medial frontal cortex (MFC) caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766, an analog of ACTH- (4-9). Wistar rats were distributed in 3 groups: MFC lesion treated with saline (M-N); MFC lesion treated with Org2766 (MO);and sham-operation treated with saline (S). Repeated Org2766 or saline injection commenced from the day of surgery and lasted for 1 3 days. After surgery. the rats were trained in a passive avoidance task and then in an active avoidance task. MFC lesions were found to be strongly associated with behavioral deficits. The M-N group rats displayed poor retention of the passive avoidance response and showed much slower learning of the active avoidance task as compared to S group rats. The result showed that chronic Org2766 administration improved the behavioral performance of both tasks in MFC lesioned rats. The also revealed that the superoxide dismutase (SOD)activity was significantly increased in the M-O group as compared to the M-N group 15 days after surgery. The possible mechanisms related to the beneficial effect of Org2766 on cortex damage are discussed.展开更多
The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (M...The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.展开更多
AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-...AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.展开更多
This study explores a novel noninvasive method for monitoring blood alfentanil concentrations using a dog model. Alfentanil which 'back', permeated across the oral mucosa from the systemic circulation was coll...This study explores a novel noninvasive method for monitoring blood alfentanil concentrations using a dog model. Alfentanil which 'back', permeated across the oral mucosa from the systemic circulation was collected from the oral mucosal surface and quantitated. The levels of the 'back' permeated alfentanil were found to closely reflect real time serum alfentanil concentrations. With further work, this finding may lead to a novel noninvasive method for monitoring real time serum alfentanil concentrations in its clinical applications.展开更多
Cytokeratin (CK) 8 mRNA expression in developing and degenerating rat prostate was studied using in situ hybridization with an antisense RNA-probe. It was found that : 1) the CK 8 antisense probe was accumulated only ...Cytokeratin (CK) 8 mRNA expression in developing and degenerating rat prostate was studied using in situ hybridization with an antisense RNA-probe. It was found that : 1) the CK 8 antisense probe was accumulated only within prostatic epithelial cells ; 2) after castration, CK 8 mRNA signals in ventral prostute(VP) sections were significantly increased, and elevated CK 8 mRNA expression persisted even long after prostate involution was complete; and 3) during prostate development,the strongest CK 8 mRNA staining was found in the early neonatal prostatic epithelia which were composed mainly of prostatic stem cells. Thereafter, a shift of CK 8 mRNA staining to peripheral regions and decreased overall CK 8 mRNA levels were noted. These data indicate that excessive expression of CK 8 mRNA is a characteristic of prostatic stem cells, and CK molecules are excellent markers for determing the hierarchical pathway of cell differentiation in prostate epithelium.展开更多
Uging diet control method to feed the weaning male Wistar rats with selenium and iodine deficiency Keshan endemic area food for 8 weeks to set up animal model. Singal channel recortling in cell attached model was used...Uging diet control method to feed the weaning male Wistar rats with selenium and iodine deficiency Keshan endemic area food for 8 weeks to set up animal model. Singal channel recortling in cell attached model was used to measure cardiac cell membrane potassium channel conductances. which coincide with the cardiac cell membrane potassium channel conductances in normal Wistar rats.The potassium channel conductance on selenlum and lodine cleficiency rat cardiac cell membrane is showing current-voltage increasing lineally in the range of clamping volatge 0±30 mV with channel conductance of 43.4 pS. The channel current does not increase depending on the clamping voltage that is showing the rectifying characteristic and the channel current amplitude can be augmented by added KIOa 5 mmol/L in bath solution. A kind of inward rectiyfing potassium channel activity was recorded, but this channel activity disappeared affer lasting 6～ 10 minutes only. Then an inward rectifying potassium channel with the conductance of 11. 2 PS was activated by KIOa 5 mmol/L, introduced to bath solution. Both conductances are less than that of normal Wistar rats.展开更多
文摘The prevalence of obesity is growing to epidemic proportions,and there is clearly a need for minimally invasive therapies with few adverse effects that allow for sustained weight loss.Behavior and lifestyle therapy are safe treatments for obesity in the short term,but the durability of the weight loss is limited.Although promising obesity drugs are in development,the currently available drugs lack efficacy or have unacceptable side effects.Surgery leads to long-term weight loss,but it is associated with morbidity and mortality.Gastric electrical stimulation(GES) has received increasing attention as a potential tool for treating obesity and gastrointestinal dysmotility disorders.GES is a promising,minimally invasive,safe,and effective method for treating obesity.External gastric pacing is aimed at alteration of the motility of the gastrointestinal tract in a way that will alter absorption due to alteration of transit time.In addition,data from animal models and preliminary data from human trials suggest a role for the gut-brain axis in the mechanism of GES.This may involve alteration of secretion of hormones associated with hunger or satiety.Patient selection for gastric stimulation therapy seems to be an important determinant of the treatment's outcome.Here,we review the current status,potential mechanisms of action,and possible future applications of gastric stimulation for obesity.
文摘Objective.The present study investigated the role of endogenous carbon monoxide(CO)in the pathogenesis of neointimal formation induced by balloon injury in rat. Method.Endothelial denudation of the left common carotid artery of rat was carried out by three passages of a Fogarty 2F balloon catheter.DNA,collagen and elastin contents of each intima media were estimated;and heme oxygenase(HO)activity and CO production in vascular smooth muscle cell(VSMC)were measured after administration of HO inhibitor. Result.Our data showed that neointima occurred in the rat on day 7 and day 21 after balloon injury,and at the same time HO activity and CO production in VSMC were markedly increased Administration of HO inhibitor,zinc deuteroporphyrin 2,4 bisglycol(ZnDPBG),could effectively inhibit HO activity and CO production,significantly enhance neointimal formation(aortic intima/media ratio were 21 4±1 8% vs 17 6±2 0%,P<0 05 on day 7;and 30 5±2 4% vs 23 0±2 2%,P<0 01 on day 21,respectively,compared with balloon alone group). Conclusion.We concluded that 1)inhibition of CO production may enhance neointimal formation induced by endothelial denudation,implying endogenous CO play an protective role in response to vascular injury,and 2)induction of HO activity may be applied clinically for preventing restenosis after angioplasty.
文摘Objective.The purpose of this study was to assess the renal graft expression of ICAM 1(intercellular adhesion molecule 1) and LFA 1(lymphocyte function associated antigen 1)molecule with relation to graft rejection. Methods.Rat kidney transplantation was performed according to the procedure of Kamada with some modification.Experimental rats were divided into 5 groups.The survival time of recipient rats and function of grafts after renal transplantation were observed.The sections of renal graft were stained for monoclonal antibody ICAM 1 and LFA 1, and then quantification of ICAM 1 and LFA 1 expression was accomplished by computer image analysis. Results.ICAM 1 and LFA 1 increased significantly in the renal allograft rejection group as compared with the non rejection groups(P<0 05). Conclusion.Both biopsy of renal graft and monitoring of ICAM 1 and LFA 1 are useful tools in diagnosing and treating acute rejection.
文摘This paper reports that lesions of the medial frontal cortex (MFC) caused behavioral deficit in rats and that this deficit could be attenuated by a well formulated treatment with Org2766, an analog of ACTH- (4-9). Wistar rats were distributed in 3 groups: MFC lesion treated with saline (M-N); MFC lesion treated with Org2766 (MO);and sham-operation treated with saline (S). Repeated Org2766 or saline injection commenced from the day of surgery and lasted for 1 3 days. After surgery. the rats were trained in a passive avoidance task and then in an active avoidance task. MFC lesions were found to be strongly associated with behavioral deficits. The M-N group rats displayed poor retention of the passive avoidance response and showed much slower learning of the active avoidance task as compared to S group rats. The result showed that chronic Org2766 administration improved the behavioral performance of both tasks in MFC lesioned rats. The also revealed that the superoxide dismutase (SOD)activity was significantly increased in the M-O group as compared to the M-N group 15 days after surgery. The possible mechanisms related to the beneficial effect of Org2766 on cortex damage are discussed.
文摘The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.
基金Supported by CLUSTER-Yoshizato Project and the National Hospital Organization Nagasaki Medical Center
文摘AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein(AFP)-producing hu-man gastric cancer cells(h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator(uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient(SCID) mouse line(uPA/SCID mice).Host mice were divided into two groups(A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index(RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A(RI = 22.0% ± 2.6%).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL(range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies(RI = 12.0% ± 6.8% and 66.0% ± 12.3%,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.
文摘This study explores a novel noninvasive method for monitoring blood alfentanil concentrations using a dog model. Alfentanil which 'back', permeated across the oral mucosa from the systemic circulation was collected from the oral mucosal surface and quantitated. The levels of the 'back' permeated alfentanil were found to closely reflect real time serum alfentanil concentrations. With further work, this finding may lead to a novel noninvasive method for monitoring real time serum alfentanil concentrations in its clinical applications.
文摘Cytokeratin (CK) 8 mRNA expression in developing and degenerating rat prostate was studied using in situ hybridization with an antisense RNA-probe. It was found that : 1) the CK 8 antisense probe was accumulated only within prostatic epithelial cells ; 2) after castration, CK 8 mRNA signals in ventral prostute(VP) sections were significantly increased, and elevated CK 8 mRNA expression persisted even long after prostate involution was complete; and 3) during prostate development,the strongest CK 8 mRNA staining was found in the early neonatal prostatic epithelia which were composed mainly of prostatic stem cells. Thereafter, a shift of CK 8 mRNA staining to peripheral regions and decreased overall CK 8 mRNA levels were noted. These data indicate that excessive expression of CK 8 mRNA is a characteristic of prostatic stem cells, and CK molecules are excellent markers for determing the hierarchical pathway of cell differentiation in prostate epithelium.
文摘Uging diet control method to feed the weaning male Wistar rats with selenium and iodine deficiency Keshan endemic area food for 8 weeks to set up animal model. Singal channel recortling in cell attached model was used to measure cardiac cell membrane potassium channel conductances. which coincide with the cardiac cell membrane potassium channel conductances in normal Wistar rats.The potassium channel conductance on selenlum and lodine cleficiency rat cardiac cell membrane is showing current-voltage increasing lineally in the range of clamping volatge 0±30 mV with channel conductance of 43.4 pS. The channel current does not increase depending on the clamping voltage that is showing the rectifying characteristic and the channel current amplitude can be augmented by added KIOa 5 mmol/L in bath solution. A kind of inward rectiyfing potassium channel activity was recorded, but this channel activity disappeared affer lasting 6～ 10 minutes only. Then an inward rectifying potassium channel with the conductance of 11. 2 PS was activated by KIOa 5 mmol/L, introduced to bath solution. Both conductances are less than that of normal Wistar rats.
