Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcript...Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.展开更多
Objective: Functional significance of NO and central inhibitory neurotransmitter γ-aminobutyric(GABA) during seizures were investigated morphorlogically. Methods: A kainate-induced complex partialseizure model was us...Objective: Functional significance of NO and central inhibitory neurotransmitter γ-aminobutyric(GABA) during seizures were investigated morphorlogically. Methods: A kainate-induced complex partialseizure model was used in our experiment. Twenty SD rats were randomly divided into KA 30, 60, 90, 200min and control groups. The brain sections were stained by NADPh (nicotinamide adenine dinucleotide phosphate ) diaphorase (Nd ) histochemically, and were further stained by GABA immunohistochemically.Results: Histological and immunohistochemical study revealed that in KA groups the number of Nd and GABA-positive double labelled neurons in CA3 region, CA3 region and dentate gyms was significantly reduced,compared with the control group. Conclusion: Nd coexisted with GABA in the brain. Reduction of GABA release led to relief of GABA-ergic inhibition and in the same way, reduction of NO release weakened its negative feedback modulation. Therefore neuronal synchronous paroxysmal discharges increased. GABA and NO,both having antiepileptic action, acted through different ways or different link in the same way. NO may involve in the effect of GABA-ergic neurons and play cooperative antiepileptic action with GABA.展开更多
Infrasound widely condition, productive exists in nature, our living and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal functio...Infrasound widely condition, productive exists in nature, our living and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motiliW and gastric morphology and to assess the expression of nitric oxide synthase （NOS） in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.展开更多
To study the effects of Siqi decoction on rats with Myocardial Ischemia, the model of Myocardium Ischemia was made for the Wistar rats cured with posterior pituitary injection through vein in tail. Siqi decoction, Dia...To study the effects of Siqi decoction on rats with Myocardial Ischemia, the model of Myocardium Ischemia was made for the Wistar rats cured with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang（DK） and Fufangdanshenpian（FD）, the latter two drugs of which were effective TCM drugs of anti-Myocardial Ischemia at present, were administrated to the rats with Myocardium Ischemia for 5 days to compare the effect of anti-Myocardium Ischemia as reference drugs by measuring the changes of NO concentration and activity of NOS in the rat blood serum with Myocardial Ischemia. There was a remarkable increase in the NO concentration and activity of NOS in serum in Siqi decoction groups compared with those in control group（p〈0.05）. The results of the prevention group in experiment of Siqi decoction are better than those of the cure group. Siqi decoction was really fit for Myocardium Ischemia via increasing NO concentration by stimulating the activity of NOS in serum. The effect of Siqi decoction against Myocardium Ischemia in preventive group is better than the curative that of Siqi decoction in the curative group.展开更多
A series of Nω-nitro-Nω’-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of amino-guanidine and nitroarginine in iNOS inhibit...A series of Nω-nitro-Nω’-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of amino-guanidine and nitroarginine in iNOS inhibition points to a potential similar utility for analogs of nitro-guanidine. The compound library was tested against the three isoforms of Nitric Oxide Synthase (eNOS, iNOS and nNOS). Several candidates showed excellent activity and good selectivity for nNOS. One particular compound even demonstrated good selectivity for iNOS. The potential usefulness of such selective inhibitors is discussed.展开更多
BACKGROUND: Some researches showed that motoneurons in spinal cord anterior horn wound die following brachial plexus injury, but the concrete mechanism of motoneurons death remains unclear. OBJECTIVE: To observe the e...BACKGROUND: Some researches showed that motoneurons in spinal cord anterior horn wound die following brachial plexus injury, but the concrete mechanism of motoneurons death remains unclear. OBJECTIVE: To observe the expression of nitric oxide synthase (NOS) and survival of C7 motoneurons in spinal cord of rats after selective brachial plexus injury. DESIGN: A randomized controlled animal experiment. SETTING:Department of Anatomy, Sun Yet-sen Medical College, Sun Yet-sen University. MATERIALS: Totally 35 adult healthy male Sprague-Dawley rats with the body mass of 200-300 g were provided by Experimental Animal Center, Sun Yet-sen Medical College, Sun Yat-sen University. The rats were divided into control group (n =5) and experimental group(n =30) by random number table method, and the experimental group was divided into three injury subgroups: anterior root avulsion group, dorsal root transection group and spinal cord hemisection group, 10 rats in each group. There were horse anti-neuronal NOS (nNOS) polycolonal antibody (Sigma company) and nicotina mideadeninedinucleotide phosphate (NADPH-d) (Sigma Company). METHODS: The experiment was performed at Department of Anatomy, Sun Yet-sen Medical College, Sun Yet-sen University between September 2004 and April 2005. ①After anesthetizing the rats, the spinous process of second thoracic vertebra as a marker, the vertebra was exposed from C5 to T1 and the lamina of vertebra was unclenched, and spinal dura mater was carved to expose the spinal nerve dorsal roots of C5-T1. The right ventral root of C7 was avulsed, and the residual root was removed in anterior root avulsion group. The right ventral root of C7 was avulsed and the right dorsal roots of brachial plexus (C5-T1) were cut off in dorsal root transection group. In spinal cord hemisection group, the hemisection between the C5 and C6 spinal segment on right side and avulsion of right ventral root of C7 were made. In the control group, the vertebra from C5 to T1 was unclenched and the skin of wound was sutured. ②Three weeks after operation, behavior of rats was observed. The rats were killed after anesthesia. The C7 segment of spinal cord was removed and treated with NADPH-d staining, neutral red counterstaining and NOS immunohistochemistry staining to detect the expression of NOS. MAIN OUTCOME MEASURES: The expression of NOS and survival of C7 motoneurons in spinal cord of rats 3 weeks after operation. RESULTS: Among the 35 included rats, 3 rats died 2 weeks following operation, so totally 32 rats were involved in the result analysis. ①NADPH-d positive neurons of in anterior horn of C7 in the three groups: The NADPH-d positive neurons could be found in anterior horn of C7 in the three groups. The percentage of that in anterior root avulsion group to that of non-injury side of spinal cord was(20.98±2.65)%, (29.43±6.81)% in dorsal root transection group and (31.74±6.80)% in spinal cord hemisection group. There was significant difference among the three injury groups(F =5.135,P =0.016). There was significant difference in anterior root avulsion group with dorsal root transection group and spinal cord hemisection group (t =2.562,3.167,P < 0.05). There was no significant difference between the dorsal root transection group and spinal cord hemisection group (P =0.534). ②survival rate of motoneurons in anterior horn of C7: There were dead motoneurons in the three injury groups, the percentages of surviving motoneurons to that of non-injured side of spinal cord were (69.22±4.04)%,(62.01±3.82)% and (56.74±6.86)%, respectively. There were significant differences among the three groups (F =9.508,P =0.002). The anterior root avulsion group was significantly different from the other two groups(t =2.764,4.587,P < 0.05). There was no significant difference between the dorsal root transection group and spinal cord hemisection group(P =0.073). CONCLUSION: The selective brachial plexus injury can induce the up-regulation of NOS expression in motorneurons of spinal cord anterior horn and block descending pathway of cortex to cause the more significant up-regulation of NOS and low survival rate in motoneurons. It indicates that descending pathway of cortex can inhibit the NOS expression in motorneurons of spinal cord anterior horn, and the high NOS expression might induce the death of motorneurons in spinal cord anterior horn.展开更多
目的:观察七龙天对低氧性肺动脉高压(HPH)大鼠内皮素-1(ET-1)、血管内皮细胞一氧化氮合成酶(NOS)的影响。方法:雄性SD大鼠随机分为6组:空白对照组(A)、模型组(B)、波生坦组(C)、七龙天低剂量组(D)、七龙天中剂量组(E)、七龙天高剂量组(F...目的:观察七龙天对低氧性肺动脉高压(HPH)大鼠内皮素-1(ET-1)、血管内皮细胞一氧化氮合成酶(NOS)的影响。方法:雄性SD大鼠随机分为6组:空白对照组(A)、模型组(B)、波生坦组(C)、七龙天低剂量组(D)、七龙天中剂量组(E)、七龙天高剂量组(F)。A组大鼠置于正常环境中饲养,B、C、D、E、F组均造模。采用常压低氧法制模,从制模第1天始给药,连续3周,A、B两组均给予蒸馏水3 m L/(只·d)。在直视下行右心导管术测定肺血流动力学参数,及RT-PCR法检测肺组织中NOS、ET-1 mRNA表达。结果:七龙天及波生坦均可明显降低大鼠肺动脉高压,且以七龙天高剂量组效果为佳,疗效呈药物剂量依赖表现。各组NOS、ET-1表达量与肺动脉压具有相关性,但二者在高剂量七龙天调节至正常范围时,肺动脉压仍未恢复正常水平。结论:不同剂量七龙天均可降低肺动脉高压,且高剂量七龙天疗效优于波生坦。其降压机制与降低NOS及ET-1表达量有关,但仍可能受其他炎症因子及血管新生因子影响。展开更多
目的:探讨血清NO及NOS在预测宫缩乏力性产后出血发生发展中的作用。方法:选择剖宫产终止妊娠的孕妇180例,因臀位、社会因素、骨盆狭窄、胎儿宫内窘迫等行剖宫产术,按产后24 h内出血量≥500 m l分为产后出血组(n=47)及非产后出血组(n=133...目的:探讨血清NO及NOS在预测宫缩乏力性产后出血发生发展中的作用。方法:选择剖宫产终止妊娠的孕妇180例,因臀位、社会因素、骨盆狭窄、胎儿宫内窘迫等行剖宫产术,按产后24 h内出血量≥500 m l分为产后出血组(n=47)及非产后出血组(n=133)。所有孕妇于剖宫产术麻醉前30 m in及术后2 h测血清NO及NOS,术中娩出胎儿后于子宫切缘上缘及胎盘母体面中央无钙化区分别取子宫肌组织及胎盘组织各一,切片作免疫组织化学分析iNOS的表达,准确收集剖宫产术中出血量及产后24 h出血量。结果:产后出血组术前、术后血清NO及NOS含量较非产后出血组明显增高,差异有显著性意义(P<0.05);血清NOS预测产后出血的灵敏度、特异度、阳性预测值、阴性预测值均高于血清NO值;从SABC免疫组化结果可见在子宫肌及胎盘均有iNOS表达,产后出血组子宫肌和胎盘的iNOS阳性表达率均显著高于非产后出血组,P<0.05;经等级相关检验,子宫肌、胎盘组织iNOS的表达强度随术前血清NO、NOS水平的升高而增加,均呈正相关。结论:血清NO、NOS水平可以正确反映子宫、胎盘NOS的活性,可作为预测宫缩乏力性产后出血的1项有效的指标。展开更多
文摘Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.
文摘Objective: Functional significance of NO and central inhibitory neurotransmitter γ-aminobutyric(GABA) during seizures were investigated morphorlogically. Methods: A kainate-induced complex partialseizure model was used in our experiment. Twenty SD rats were randomly divided into KA 30, 60, 90, 200min and control groups. The brain sections were stained by NADPh (nicotinamide adenine dinucleotide phosphate ) diaphorase (Nd ) histochemically, and were further stained by GABA immunohistochemically.Results: Histological and immunohistochemical study revealed that in KA groups the number of Nd and GABA-positive double labelled neurons in CA3 region, CA3 region and dentate gyms was significantly reduced,compared with the control group. Conclusion: Nd coexisted with GABA in the brain. Reduction of GABA release led to relief of GABA-ergic inhibition and in the same way, reduction of NO release weakened its negative feedback modulation. Therefore neuronal synchronous paroxysmal discharges increased. GABA and NO,both having antiepileptic action, acted through different ways or different link in the same way. NO may involve in the effect of GABA-ergic neurons and play cooperative antiepileptic action with GABA.
基金financially supported by the Shaanxi province science and technology project[grant number 2005k12-G1-3]
文摘Infrasound widely condition, productive exists in nature, our living and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motiliW and gastric morphology and to assess the expression of nitric oxide synthase （NOS） in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.
基金Natural Science Foundation of Jilin Province, China(No.20050561)
文摘To study the effects of Siqi decoction on rats with Myocardial Ischemia, the model of Myocardium Ischemia was made for the Wistar rats cured with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang（DK） and Fufangdanshenpian（FD）, the latter two drugs of which were effective TCM drugs of anti-Myocardial Ischemia at present, were administrated to the rats with Myocardium Ischemia for 5 days to compare the effect of anti-Myocardium Ischemia as reference drugs by measuring the changes of NO concentration and activity of NOS in the rat blood serum with Myocardial Ischemia. There was a remarkable increase in the NO concentration and activity of NOS in serum in Siqi decoction groups compared with those in control group（p〈0.05）. The results of the prevention group in experiment of Siqi decoction are better than those of the cure group. Siqi decoction was really fit for Myocardium Ischemia via increasing NO concentration by stimulating the activity of NOS in serum. The effect of Siqi decoction against Myocardium Ischemia in preventive group is better than the curative that of Siqi decoction in the curative group.
文摘A series of Nω-nitro-Nω’-substituted guanidines has been prepared as potential inhibitors of the human Nitric Oxide Synthase (NOS) isoforms. The reported utility of amino-guanidine and nitroarginine in iNOS inhibition points to a potential similar utility for analogs of nitro-guanidine. The compound library was tested against the three isoforms of Nitric Oxide Synthase (eNOS, iNOS and nNOS). Several candidates showed excellent activity and good selectivity for nNOS. One particular compound even demonstrated good selectivity for iNOS. The potential usefulness of such selective inhibitors is discussed.
文摘BACKGROUND: Some researches showed that motoneurons in spinal cord anterior horn wound die following brachial plexus injury, but the concrete mechanism of motoneurons death remains unclear. OBJECTIVE: To observe the expression of nitric oxide synthase (NOS) and survival of C7 motoneurons in spinal cord of rats after selective brachial plexus injury. DESIGN: A randomized controlled animal experiment. SETTING:Department of Anatomy, Sun Yet-sen Medical College, Sun Yet-sen University. MATERIALS: Totally 35 adult healthy male Sprague-Dawley rats with the body mass of 200-300 g were provided by Experimental Animal Center, Sun Yet-sen Medical College, Sun Yat-sen University. The rats were divided into control group (n =5) and experimental group(n =30) by random number table method, and the experimental group was divided into three injury subgroups: anterior root avulsion group, dorsal root transection group and spinal cord hemisection group, 10 rats in each group. There were horse anti-neuronal NOS (nNOS) polycolonal antibody (Sigma company) and nicotina mideadeninedinucleotide phosphate (NADPH-d) (Sigma Company). METHODS: The experiment was performed at Department of Anatomy, Sun Yet-sen Medical College, Sun Yet-sen University between September 2004 and April 2005. ①After anesthetizing the rats, the spinous process of second thoracic vertebra as a marker, the vertebra was exposed from C5 to T1 and the lamina of vertebra was unclenched, and spinal dura mater was carved to expose the spinal nerve dorsal roots of C5-T1. The right ventral root of C7 was avulsed, and the residual root was removed in anterior root avulsion group. The right ventral root of C7 was avulsed and the right dorsal roots of brachial plexus (C5-T1) were cut off in dorsal root transection group. In spinal cord hemisection group, the hemisection between the C5 and C6 spinal segment on right side and avulsion of right ventral root of C7 were made. In the control group, the vertebra from C5 to T1 was unclenched and the skin of wound was sutured. ②Three weeks after operation, behavior of rats was observed. The rats were killed after anesthesia. The C7 segment of spinal cord was removed and treated with NADPH-d staining, neutral red counterstaining and NOS immunohistochemistry staining to detect the expression of NOS. MAIN OUTCOME MEASURES: The expression of NOS and survival of C7 motoneurons in spinal cord of rats 3 weeks after operation. RESULTS: Among the 35 included rats, 3 rats died 2 weeks following operation, so totally 32 rats were involved in the result analysis. ①NADPH-d positive neurons of in anterior horn of C7 in the three groups: The NADPH-d positive neurons could be found in anterior horn of C7 in the three groups. The percentage of that in anterior root avulsion group to that of non-injury side of spinal cord was(20.98±2.65)%, (29.43±6.81)% in dorsal root transection group and (31.74±6.80)% in spinal cord hemisection group. There was significant difference among the three injury groups(F =5.135,P =0.016). There was significant difference in anterior root avulsion group with dorsal root transection group and spinal cord hemisection group (t =2.562,3.167,P < 0.05). There was no significant difference between the dorsal root transection group and spinal cord hemisection group (P =0.534). ②survival rate of motoneurons in anterior horn of C7: There were dead motoneurons in the three injury groups, the percentages of surviving motoneurons to that of non-injured side of spinal cord were (69.22±4.04)%,(62.01±3.82)% and (56.74±6.86)%, respectively. There were significant differences among the three groups (F =9.508,P =0.002). The anterior root avulsion group was significantly different from the other two groups(t =2.764,4.587,P < 0.05). There was no significant difference between the dorsal root transection group and spinal cord hemisection group(P =0.073). CONCLUSION: The selective brachial plexus injury can induce the up-regulation of NOS expression in motorneurons of spinal cord anterior horn and block descending pathway of cortex to cause the more significant up-regulation of NOS and low survival rate in motoneurons. It indicates that descending pathway of cortex can inhibit the NOS expression in motorneurons of spinal cord anterior horn, and the high NOS expression might induce the death of motorneurons in spinal cord anterior horn.
文摘目的:观察七龙天对低氧性肺动脉高压(HPH)大鼠内皮素-1(ET-1)、血管内皮细胞一氧化氮合成酶(NOS)的影响。方法:雄性SD大鼠随机分为6组:空白对照组(A)、模型组(B)、波生坦组(C)、七龙天低剂量组(D)、七龙天中剂量组(E)、七龙天高剂量组(F)。A组大鼠置于正常环境中饲养,B、C、D、E、F组均造模。采用常压低氧法制模,从制模第1天始给药,连续3周,A、B两组均给予蒸馏水3 m L/(只·d)。在直视下行右心导管术测定肺血流动力学参数,及RT-PCR法检测肺组织中NOS、ET-1 mRNA表达。结果:七龙天及波生坦均可明显降低大鼠肺动脉高压,且以七龙天高剂量组效果为佳,疗效呈药物剂量依赖表现。各组NOS、ET-1表达量与肺动脉压具有相关性,但二者在高剂量七龙天调节至正常范围时,肺动脉压仍未恢复正常水平。结论:不同剂量七龙天均可降低肺动脉高压,且高剂量七龙天疗效优于波生坦。其降压机制与降低NOS及ET-1表达量有关,但仍可能受其他炎症因子及血管新生因子影响。
文摘目的:探讨血清NO及NOS在预测宫缩乏力性产后出血发生发展中的作用。方法:选择剖宫产终止妊娠的孕妇180例,因臀位、社会因素、骨盆狭窄、胎儿宫内窘迫等行剖宫产术,按产后24 h内出血量≥500 m l分为产后出血组(n=47)及非产后出血组(n=133)。所有孕妇于剖宫产术麻醉前30 m in及术后2 h测血清NO及NOS,术中娩出胎儿后于子宫切缘上缘及胎盘母体面中央无钙化区分别取子宫肌组织及胎盘组织各一,切片作免疫组织化学分析iNOS的表达,准确收集剖宫产术中出血量及产后24 h出血量。结果:产后出血组术前、术后血清NO及NOS含量较非产后出血组明显增高,差异有显著性意义(P<0.05);血清NOS预测产后出血的灵敏度、特异度、阳性预测值、阴性预测值均高于血清NO值;从SABC免疫组化结果可见在子宫肌及胎盘均有iNOS表达,产后出血组子宫肌和胎盘的iNOS阳性表达率均显著高于非产后出血组,P<0.05;经等级相关检验,子宫肌、胎盘组织iNOS的表达强度随术前血清NO、NOS水平的升高而增加,均呈正相关。结论:血清NO、NOS水平可以正确反映子宫、胎盘NOS的活性,可作为预测宫缩乏力性产后出血的1项有效的指标。
