Effect of nicardipine on learning and memory in mice

AIM: To study if nicardipine could improve learning and memory in mice. METHODS AND RESULTS: Nicardipine (0.5mg·kg~(-1)or 0.2 mg·kg~(-1), po) was shown to improve learning and memory in Y mize in mice, which increased passive avoidane response. Nicardipine was capable of antagonizing pentobarbital (15 mg·kg~(-1), ip)-in     

Effect of telmisartan on expression of protein kinase C-α in kidneys of diabetic mice

Aim： To investigate the effects of angiotensin receptor blocker （ARB） telmisartan on the expression and distribution of protein kinase C （PKC）-α in the kidneys of diabetic mice. Methods： Diabetic mice were induced with streptozotocin and a group of them were randomly selected for treatment with telmisartan. After 6 weeks, the expression and localization of PKC-α in the renal cortex, and the outer and inner medulla were assessed by immunohistochemistry and semiquantitative Western blotting. In addition, expressions of PKC-α, transforming growth factor- β1 （TGF-β1）, and vascular endothelial growth factor （VEGF） in glomeruli were measured by semiquantitative immunohistochemistry. Results： Diabetic and normal mice showed similar distributions of PKC-α in the kidneys. The expression of PKC-α was found in glomeruli, epithelial cells of proximal tubules, and medullary- collecting duct, while not in the medullary and cortical thick ascending limb, and was different in the epithelial cells of proximal tubules of diabetic nephropathy （DN） mice, PKC-α was mostly translocated from the basement membrane to the apical membrane, whereas it was largely translocated from the apical membrane to the basement membrane in epithelial cells of the inner medullary-collecting duct. Western blotting detected increased expression of PKC-α in the renal cortex and outer medulla, but not in the inner medulla of DN mice. Enhanced expressions of PKC-α, TGF-β1, and VEGF were shown in the glomeruli of DN mice, where PKC-α exhibited a correlation to VEGF, but no correlation to TGF-β1. ARB telmisartan attenuated alterations of PKC-α as mentioned earlier in the DN mice. Conclusion： Our findings suggest that PKC-α may play a role in the pathogenesis of DN, and that the nephroprotective effects of ARB telmisartan may be partly associated with its influence on PKC-α.     

Effect of catecholamic acid on detoxication and distribution of NiCl_2 in mice and rats

目的：研究双酚胺酸（ＣＢＭＩＤＡ）对氯化镍的解毒作用．方法：ＮｉＣｌ２中毒后，立即给予ＣＢＭＩＤＡ，记录动物存活数；小鼠ｉｖ６３ＮｉＣｌ２后给药，测定２４ｈ组织中６３镍；用整体放射自显影术，显示小鼠体内６３镍分布．结果：ｓｃＣＢＭＩＤＡ０５－１５ｇ·ｋｇ－１对ｉｐＮｉＣｌ２５００ｍｇ·ｋｇ－１有解毒作用；小鼠ｉｐＮｉＣｌ２ＬＤ５０为８２８ｍｇ·ｋｇ－１，给药１５或２５ｇ·ｋｇ－１，ＬＤ５０分别为７８９和８２０ｍｇ·ｋｇ－１；大鼠ｉｍＣＢＭＩＤＡ５００ｍｇ·ｋｇ－１使ＮｉＣｌ２的ＬＤ５０提高８倍；组织中６３镍测定和定位显示，ＣＢＭＩＤＡ减少肺和血液中６３镍，增加了骨中６３镍，２４ｈ尿、粪６３镍排出与对照组无明显差异．结论：ＣＢＭＩＤＡ有效地解除镍毒性，提高动物存活率，降低镍在肺部的滞留．     

Effect of Fusheng Capsules on Cerebral Ischemia tolerability in mice

Objective：To explore the effect of Fusheng Capsules on the anoxia tolerability in experimental cerebral ischemia in mice. Methods： The gasp time and survival time of mice were observed after de capitation on mouse decapitation model and the model of ligation of bilateral common carotid artery. Clotting time and MDA content in brain tissue were determined with slide method and colorimetric method, respectively.     

Effect of IRE1α knockdown on gut development

目的 探讨肌醇酶1α(IRE1α)在非洲爪蟾胚胎发育中的作用.方法 利用全胚胎原位杂交法检测IRE1α在胚胎发育晚期的表达;设计合成特异性封闭IRE1α的反义寡核苷酸(MO),通过显微注射方法实现基因封闭.结果 IRE1α在胚胎发育晚期高表达于胰腺.在体外翻译系统中,IRE1αMO可以阻断IRE1α蛋白质的合成.封闭IRE1α对胚胎发育早期无明显影响;但在发育晚期导致肠道结构消失,胚胎发育明显异常.结论 IRE1α对非洲爪蟾胚胎发育早期无影响,但在晚期导致肠道发育异常.     

Effects of 2.5 s mouse nerve growth factor on regeneration of injured sciatic nerves in mice and rats

目的：证实ＮＧＦ促进坐骨神经再生的作用．方法：夹断小鼠和大鼠坐骨神经轴索，测再生轴索计数及分类，在比目鱼肌远（Ｄｉｓ）、近（Ｐｒｏ）端测神经肌肉电潜伏期（ＮＭＥＰＬ）．结果：小鼠ＮＧＦｉｍ０５－１ｋＢＵ·ｋｇ－１２０ｄ增加轴索再生率，２－４ｋＢＵ·ｋｇ－１减轻比目鱼肌萎缩．大鼠ＮＧＦｉｍ１（４０ｄ），２（３０和４０ｄ），４（２０，３０，４０ｄ）ｋＢＵ·ｋｇ－１均显著增加损伤神经的轴索再生率；高、中剂量增加粗轴索计数；各剂量均缩短ＤｉｓＮＭＥＰＬ（２０ｄ，３０ｄ）和ＰｒｏＮＭＥＰＬ（４０ｄ）；高剂量在各时点使两者均缩短．结论：ＮＧＦｉｍ明显促进大鼠和小鼠坐骨神经损伤后再生并减轻骨骼肌萎缩．     

Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

OBJECTIVE To investigate the effect ofα-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. METHODS A mouse model of impaired learning and memory was created by ethanol(2.0 g · kg~(-1), ig). α-Asarone(7.5, 15 and 30 mg·kg~(-1), ip) was delivered 10 min prior to ethanol administration. After 40 min, the locomotor activity of mice with learning and memory impairment was evaluated by the open field test and the behavioral effect of α-asarone was evaluated using the novel object recognition test.Glutamate(Glu) and γ-aminobutyric acid(GABA) levels in the hippocampus were determined by ELISA, and the proteins expression levels of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor(Glu R2), N-methyl-D-aspartic acid(NMDA)receptor(NMDAR2 B), synaptophysin I(SYNΙ), glutamate transporter type 1(GLT-1) and calcium/calmodulindependent protein kinaseⅡ(Ca MKⅡ) were detected by Western blotting. RESULTS There was no significant difference in the horizontal or vertical locomotor activity between the ethanol and normal groups or the 7.5, 15 and 30 mg·kg~(-1)α-asarone groups[F(5, 48)=0.6536, P>0.05; F(5, 49)=1.995, P>0.05]. The recognition index in the ethanol group was significantly decreased as compared with that in the normal group[F(5, 46) =6.739, P<0.05]and was markedly increased in the α-asarone groups as compared with that in the ethanol group(P<0.05), with the exception of the 7.5 mg · kg~(-1)α-asarone group(P>0.05). The hippocampal Glu: GABA ratio in mice was significantly elevated in the ethanol group as compared with that in the normal group(33.42±0.8972 vs 30.79±0.2102, P<0.05) and significantly lower in the α-asarone groups(31.99±0.4986 vs. 33.42±0.8972; 30.97±0.1757 vs. 33.42±0.8972; 30.83 0.1723 vs. 33.42±0.8972, P<0.05). The expression levels of GluR2, NMDAR2B, pSYNⅠand p Ca MKII were significantly higher in the ethanol group as compared with those in the normal group(P<0.05) and obviously lower in the α-asarone groups(P<0.05), with the exception of GluR2, NMDAR2B and pCaMKⅡ in the 7.5 mg·kg~(-1)α-asarone group(P>0.05).And the expression level of GLT-1 was significantly lower in the ethanol group as compared with that in the normal group(P<0.05) and obviously higher in the α-asarone groups(P<0.05). CONCLUSION Pretreatment with α-asarone significantly improved the learning and memory impairment. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.     

Effect of artemether on glyceraldehyde-3-phosphate dehydrogenase,phosphogly-cerate kinase,and pyruvate kinase of Schistosoma japonicum harbored in mice

目的：研究蒿甲醚（Ａｒｔ）对日本血吸虫３磷酸甘油醛脱氢酶（ＧＡＰＤＨ）、磷酸甘油酸激酶（ＰＧＫ）和丙酮酸激酶（ＰＫ）的影响．方法：小鼠感染血吸虫尾蚴３２－３８ｄ后ｉｇＡｒｔ１００－３００ｍｇ·ｋｇ－１，２４－７２ｈ后取虫测定上述３种酶和乳酸含量．结果：小鼠ｉｇＡｒｔ３００ｍｇ·ｋｇ－１后２４－４８ｈ，血吸虫♀、♂虫的ＰＧＫ和ＰＫ活力被抑制２７％－４８％；♀虫的ＧＡＰＤＨ对Ａｒｔ亦较敏感，♂虫则否．给药后７２ｈ，♀虫乳酸含量降低７２％，♂虫的降低４９％．结论：Ａｒｔ对血吸虫的ＰＧＫ和ＰＫ活力有明显抑制作用，♀虫的ＧＡＰＤＨ对Ａｒｔ亦较敏感，♀虫乳酸含量降低较♂虫明显     

Effect of α7 nicotinic acetylcholine receptor agonists and antagonists on motor function in mice

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline.     

Clinical significance of the expression of HIF-1α and VEGF gene in endometrial carcinoma tissue

Objective To explore the relationship between the expression of HIF-1 alpha,VEGF gene and cliulcal stage of endometrial cancer. Methods 30 patients with the membrane carcinoma were detected VEGF, HIF-1α expression by immunohistochemical method. The expression of different pathological type and clinical stage were analyzed. Another 10 pieces achieved from endometriosis dysplasia organization were taken as control. Results The positive rate of HIF-1 alpha, VEGF in endometriosis dysplasia and endometrial carcinoma were statistically significant differences( x2=11.87,8. 71, all P ＜ 0. 05 );There was correlated relationship between ultrasonic grading of tumor blood and HIF-1 alpha, VEGF; There was correlated relationship between Lesions and HIF-1 alpha, VEGF.Conclusion The expressions of HIF-1 alpha, VEGF were positively correlated to the degree,metastasis and prognosis of malignant endometrial carcinoma.     

Effect of Liposomal and Free Bisphosphonates on the IL-1β, IL-6 and TNFα Secretion from RAW 264 Cells in Vitro

Purpose. In order to evaluate the possible antiinflammatory action of bisphosphonates, the effect of the drugs on the secretion of proinflammatory cytokines (IL-l, IL-6 and TNF) from macrophages was studied. Liposomes or high concentration of extracellular calcium was used to enhance the intracellular delivery of bisphosphonates. Methods. RAW 264 cells were used as macrophage model, and they were induced with lipopolysaccharide to produce the cytokines. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay. Results. As a free drug, clodronate and pamidronate, but not etidronate, inhibited LPS-stimulated secretion of the cytokines from macrophage-like RAW 264 cells. Low concentrations of pamidronate, however, induced the IL-6 secretion, and the cytokine inhibitory action at the higher concentrations of pamidronate was attributed to cytotoxicity of the compound. The cytokine induction or toxic effects were not observed with clodronate or etidronate. When the drugs were encapsulated in negatively charged unilamellar liposomes, the inhibitory potency of both clodronate and etidronate enhanced by a factor of 10-20, while that of pamidronate was not increased. The complex formation of bisphosphonates with extracellular calcium, although enhancing the uptake of the compounds by macrophages, did not considerably increase their cytokine inhibitory potency. Conclusions. Bisphosphonates have inhibitory action on cytokine secretion by macrophages. The non-cytotoxic cytokine inhibition by liposome encapsulated clodronate could be beneficial in local inflammatory diseases, where the inflammation is sustained by the excessive amounts of inflammatory cytokines produced by activated macrophages.     

Effect of inorganic active element on hypoxia inducing factor-1α and cytokines in chronic ulcer tissue in rats and its action mechanism

目的 检测无机活性元素(德莫林)对大鼠皮肤慢性溃疡组织的影响,并对其作用机制进行分析.方法 制备SD大鼠慢性溃疡模型,实验组应用无机活性元素,对照组常规消毒换药,另设空白组.观察3组溃疡的愈合时间.应用RT-PCR技术对3组溃疡组织乏氧诱导因子(HIF)-1α、表皮细胞生长因子(EGF)、碱性成纤维细胞因子(bFGF)、血管内皮细胞生长因子(VEGF)的表达进行检测,并对其差异进行比较分析.结果 与对照组比较,实验组创面面积缩小更为明显(P＜0.05);实验组、对照组的HIF-1α、EGF、bFGF和VEGF表达均明显高于正常皮肤(P＜0.05),实验组EGF、bFGF和VEGF表达高于对照组,而HIF-1α表达低于对照组(P＜0.05).结论 无机活性元素对慢性溃疡的治疗效果优于传统换药方法,其机制与该药物能促进EGF、bFGF和VEGF表达、抑制HIF-1α表达有关.     

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing 1??Gd-DTPA-BMA in Ehrlich tumor bearing mice

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the 1??Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer.     

Effects of aluminum potassium sulfate on learning,memory,and cholinergic system in mice

目的：研究硫酸铝钾中的铝对正常及ＡＦ６４Ａ小鼠学习、记忆的影响．方法：被动回避反射仪测避暗潜伏期（ＳＴＬ）；原子吸收分光光度法测血、脑铝；化学发光法测脑乙酰胆碱（ＡＣｈ）；放射化学法测脑胆碱乙酰基转移酶（ＣｈＡＴ）．结果：１ｇ·ｋｇ－１组３０日时，血脑铝升高；６０日伴ＳＴＬ、ＡＣｈ、ＣｈＡＴ分别下降４６４％，８５％，２２６％；９０日ＳＴＬ、ＡＣｈ、ＣｈＡＴ分别下降５００％，１１１％和２７８％．０２５ｇ·ｋｇ－１只有血铝升高．１ｇ·ｋｇ－１使ＡＦ６４Ａ模型小鼠血、脑铝升高，其他无改变．结论：硫酸铝钾１ｇ·ｋｇ－１·ｄ－１６０日使小鼠学习、记忆障碍及胆碱能系统改变     

Which is most sensitive? Assessing responses of mice and rats in toxicity bioassays

Rodent species are commonly used in traditional toxicology testing guidelines to predict human health toxicity outcomes. The use of a consistent species in test guidelines is important for maintaining consistency and comparability between tests and testing guidelines. This recommendation was operationalized for this study as the implicit assumption of uniform species and species-sex sensitivities. This investigation analyzed the uniformity assumption using data from National Toxicology Program Technical Reports (and where applicable Toxicity Reports), which provide data from both short-term and chronic rodent toxicity tests. These data were extracted and modeled using the Environmental Protection Agency’s Benchmark Dose Software. Minimum best-fit benchmark doses (BMD) and benchmark dose lower limits (BMDL) were determined and a minimum best-fit BMD10 and BMDL10 estimated for every chemical and study duration. Endpoints of interest included non-neoplastic lesions, final mean body weights, and mean organ weights. The distribution of findings was then assessed to determine the most sensitive species and species-sex combinations associated with the minimum best-fit BMDL10. Data indicated that species and species-sex sensitivity for this group of chemicals is not uniform and that rats are significantly more sensitive than mice for non-cancerous outcomes observed, depending upon study duration. There are also indications that male rats may be more sensitive than other species-sex groups in certain situations.