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Comparison of behavioural and molecular effects of two different schizophrenia models induced by subchronic MK-801 administration in rats 亚慢性MK-801对两种不同精神分裂症模型大鼠行为和分子效应的比较
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.57
G. Unal, F. Aricioglu
Schizophrenia is a severe psychiatric disorder with about 1% prevalance. NMDA receptor antagonists such as Phencyclidine (PCP) and MK-801 are commonly used for modeling schizophrenia in rodents. In literature, despite of the concensus about subchronic PCP administration (commonly 7 days, bi-daily administration followed by a 1 week washout period), there are different subchronic administration regimens for MK-801 beside 7 days, bidaily (MK-801-7), such as 14 days (MK-801-14) daily or 28 days daily injections. In this study, we aimed to compare two prevalant MK-801 models (MK-801-7 and MK-801-14, 0.2 mg/kg) in both behavioural and molecular changes. Wistar Hannover rats grouped as control (n=10), MK-801-14 (n=8) and MK-801-7 (n=8). Prepulse inhibition of acustic startle response (PPI), novel object recognition test (NORT), social interaction (SI) and Morris's water maze (MWM) tests were used for behavioural analyzes while real time polimerase chain reaction (Rt-PCR) was conducted for molecular analyzes of glutamic acid decarboxilase 67 (GAD67) and parvalbumin. Our results showed decreased PPI in MK-801-14 and MK801-7 groups. Moreover, in both models platform finding latencies were increased and swimming time in platform area was decreased in MWM. MK-801-14 and MK-801-7 reduced following and raised avoiding behaviours in SI. In Rt-PCR, GAD67 mRNA levels were decreased by MK-801-14 and MK-801-7 administrations. However, only MK-801-7 decreased discrimination index in NORT and parvalbumin mRNA levels. In this study, it has been showed that although MK-801-14 and MK-801-7 administrations revealed smiliar schizophrenia like symptoms in rats, MK-801-7 has partial superiories in certain aspects.
精神分裂症是一种严重的精神疾病,患病率约为1%。NMDA受体拮抗剂如苯环利定(PCP)和MK-801通常用于模拟啮齿动物的精神分裂症。在文献中,尽管对PCP亚慢性给药(通常是7天,每天两次给药,然后是1周的洗脱期)有共识,但MK-801的亚慢性给药方案除了7天,每天两次(MK-801-7),如每天14天(MK-801-14)或每天28天注射。在这项研究中,我们旨在比较两种流行的MK-801模型(MK-801-7和MK-801-14, 0.2 mg/kg)的行为和分子变化。Wistar汉诺威大鼠分为对照组(n=10)、MK-801-14大鼠(n=8)和MK-801-7大鼠(n=8)。行为学分析采用脉冲前抑制声惊反应(PPI)、新目标识别测试(NORT)、社会互动(SI)和Morris水迷宫(MWM)测试,实时聚合酶链反应(Rt-PCR)分析谷氨酸脱羧酶67 (GAD67)和小白蛋白。我们的结果显示MK-801-14和MK801-7组PPI下降。此外,两种模型都增加了平台寻找潜伏期,减少了平台区域的游泳时间。MK-801-14和MK-801-7减少了SI中的跟随行为,提高了回避行为。在Rt-PCR中,MK-801-14和MK-801-7处理后,GAD67 mRNA水平降低。然而,只有MK-801-7降低了NORT和小白蛋白mRNA水平的区分指数。本研究表明,虽然MK-801-14和MK-801-7在大鼠中表现出类似的精神分裂症样症状,但MK-801-7在某些方面具有部分优势。
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引用次数: 2
Nephroprotective effect of cerium oxide nanoparticles on cyclophosphamide-induced nephrotoxicity via anti-apoptotic and antioxidant properties in BALB/c mice 氧化铈纳米颗粒通过抗凋亡和抗氧化作用对环磷酰胺引起的BALB/c小鼠肾毒性的保护作用
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.55
M. Hamzeh, F. Amiri, S. Y. Beklar, S. Hosseinimehr
Cyclophosphamide [CP], as alkylating agents has side effects such as nephrotoxicity. Cerium oxide nanoparticles [nanoceria; NC], as an antioxidant, are effective at reduction oxidative stress. This study evaluated the protective effect of nanoceria in nephrotoxicity induced CP. 32 BALB/c mice were randomly divided into four equal groups. Control, NC, CP and NC+CP. NC and CP injected intraperitoneally respectively in dose of 100 μg/kg for 3 days and 200 mg/kg single dose on 3th day of study. Two days after the final treatment, histochemical, serum biochemical, histopathological and immunohistochemical examinations were performed for determination effects of NC on nephrotoxicity. Oxidative stress and renal injury induced in CP treated mice were proved by the significantly elevation of urea and creatinine and alteration in oxidative stress markers [MDA and GSH levels]. Consequently, histopathological changes and apoptosis were markedly increased. NC was able to reduce MDA, urea , creatinine and increase GSH content. In addition, NC pretreatment could alleviated immunoreactivity of caspase-3. NC revealed a strong antioxidant in nephrotoxicity following CP treatment. This study suggests that NC through antioxidant and antiapoptotic properties have protective effect against CP-induced nephrotoxicity.
环磷酰胺[CP]作为烷基化剂具有肾毒性等副作用。氧化铈纳米粒子;NC]作为一种抗氧化剂,在减少氧化应激方面是有效的。本研究以32只BALB/c小鼠为实验对象,随机分为4组,观察纳米粒对肾毒性CP的保护作用。Control, NC, CP和NC+CP。NC和CP分别以100 μg/kg的剂量腹腔注射3天,第3天单次给药200 mg/kg。末次治疗2 d后行组织化学、血清生化、组织病理及免疫组织化学检查,测定NC对肾毒性的影响。通过尿素和肌酐的显著升高以及氧化应激标志物[MDA和GSH水平]的改变,证实了CP处理小鼠引起的氧化应激和肾损伤。因此,组织病理学改变和细胞凋亡明显增加。NC能降低MDA、尿素、肌酐,提高GSH含量。此外,NC预处理可以减轻caspase-3的免疫反应性。在CP治疗后,NC显示出较强的抗氧化作用。本研究提示NC通过抗氧化和抗凋亡特性对cp所致肾毒性具有保护作用。
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引用次数: 16
Reporting long-term effects of metabolic stress on human ovary carcinoma 报告代谢应激对人卵巢癌的长期影响
Pub Date : 2018-04-06 DOI: 10.12991/mpj.2018.52
M. Nakhjavani, F. Shirazi
A key challenge in cancer treatment is the wide range of cancer cells’ behavior towards chemotherapy and treatment procedures, which makes the outcomes of treatment often unpredictable, accompanied by cancer resistance and recurrence. One underlying reason is that tumor is a heterogeneous tissue. The cells within a tumor are at different metabolic states and hence behave differently from another and towards the chemotherapeutics. Many of the cells in the inner layers of a tumor lack an appropriate growth condition. However, upon tumor shrinkage, they can regrow and finally cause tumor resistance or recurrence. In the current study, for the first time, long term effects of different levels of metabolic stress on human ovary cancer cell line, A2780, is reported. In this in vitro model, the cells exposed to 10% serum were considered as control and metabolic stress was induced at 0.5, 0.25 and 0% serum for 1-6 days. In this 6-day period, cells’ morphology changes, size, cell cycle, mitochondrial function and protein content was measured at 24-hour intervals. Also, cells ability to recur was assessed with the above tests in a 24-hour release in 10% serum. The results of this study showed that A2780 cells show resistant features against metabolic stress and this longterm stress does not stop cells recurrence. These results indicate that in order to have a successful tumor treatment, a modified chemotherapy procedures against different types of cells laying within one tumor is required.
癌症治疗的一个关键挑战是癌细胞对化疗和治疗程序的广泛行为,这使得治疗结果往往不可预测,伴随着癌症抵抗和复发。一个潜在的原因是肿瘤是一种异质组织。肿瘤内的细胞处于不同的代谢状态,因此对化疗药物的反应也不同。肿瘤内层的许多细胞缺乏适当的生长条件。然而,在肿瘤缩小后,它们可以重新生长,最终导致肿瘤抵抗或复发。本研究首次报道了不同水平的代谢应激对人卵巢癌细胞系A2780的长期影响。在体外模型中,以10%血清浓度的细胞为对照,分别在0.5%、0.25和0%血清浓度下诱导代谢应激1 ~ 6 d。在这6 d期间,每隔24小时测量细胞形态变化、大小、细胞周期、线粒体功能和蛋白质含量。同时,在10%血清中24小时释放,用上述试验评估细胞复发能力。本研究结果表明,A2780细胞对代谢应激具有抵抗性,这种长期应激并不能阻止细胞复发。这些结果表明,为了成功治疗肿瘤,需要一种针对同一肿瘤内不同类型细胞的改良化疗程序。
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引用次数: 1
Effect of exposure time and smoking habit on arsenic levels in biological samples of metal workers in comparison with controls 接触时间和吸烟习惯对金属工人生物样品中砷含量的影响
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.59
B. Yüksel, Nilgün Şen, V. A. Türksoy, E. Tutkun, T. Söylemezoğlu
The main goal of this study was to investigate the effect of exposure time and smoking habit on arsenic levels in biological samples of workers occupationally exposed to metals in comparison with non-occupational residents in Turkey. Blood, urine and hair samples were collected from 95 metal workers at Ankara Occupational Diseases Hospital, Turkey. Similarly, 94 hair samples were taken from controls. Arsenic levels in biological samples were measured using Graphite Furnace Atomic Absorption Spectrometry (GFAAS) equipped with Zeeman background correction and Hydride Generation Atomic Absorption Spectrometry (HGAAS). In metal workers; mean hair-arsenic levels of the smokers group (2.05 ±1.97 mg As/kg) was found to be significantly higher than the mean of the hair-arsenic levels of non-smokers group 1.80±1.79 mg As/kg (p<0.05). Mean hair-arsenic levels of exposure time group (4-10 years) was found (2.34±2.21 mg As/kg) to be significantly higher than the arithmetic mean of exposure time group (1-3 years) (1.39 ±1.25 mg As/kg, p<0.01). As for the control group, mean of hair-arsenic levels in the smokers group (0.133 ±0.012 mg As/kg) was found to be significantly higher than the mean of the hair-arsenic levels of non-smokers group (0.101±0.006 mg As/kg, p<0.05). In addition, mean hair arsenic level in metal workers (1.81 ±1.79 mg As/kg) was found significantly higher than mean hair arsenic level in control group (0.115 ±0.006 mg As/kg, p=0.00). Smoking increased the hair arsenic levels significantly both in metal workers and controls. The hair arsenic levels significantly enhanced with ascending exposure time. In addition, metal workers had significantly higher hair arsenic levels than controls. However, there was no significant effect detected in terms of urine and blood arsenic levels.
本研究的主要目的是调查接触时间和吸烟习惯对接触金属的职业工人与非职业居民生物样本中砷水平的影响。在土耳其安卡拉职业病医院收集了95名金属工人的血液、尿液和头发样本。同样,从对照组中提取了94份头发样本。采用塞曼背景校正石墨炉原子吸收光谱法(GFAAS)和氢化物发生原子吸收光谱法(HGAAS)测定生物样品中的砷含量。金属工人;吸烟组平均发砷水平(2.05±1.97 mg As/kg)显著高于不吸烟组平均发砷水平(1.80±1.79 mg As/kg) (p<0.05)。暴露时间组(4 ~ 10年)平均发砷水平(2.34±2.21 mg As/kg)显著高于暴露时间组(1 ~ 3年)的算术平均值(1.39±1.25 mg As/kg, p<0.01)。对照组中,吸烟组发砷含量平均值(0.133±0.012 mg As/kg)显著高于不吸烟组发砷含量平均值(0.101±0.006 mg As/kg, p<0.05)。金属工人发砷平均水平(1.81±1.79 mg As/kg)显著高于对照组(0.115±0.006 mg As/kg, p=0.00)。吸烟大大增加了金属工人和对照组头发中的砷含量。头发砷含量随暴露时间的增加而显著增加。此外,金属工人的头发砷含量明显高于对照组。然而,在尿液和血液中的砷含量方面没有发现明显的影响。
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引用次数: 14
QSAR studies of novel iminochromene derivatives as as carbonyl reductase 1 (CBR1) inhibito 新型亚胺衍生物与羰基还原酶1 (CBR1)抑制剂的QSAR研究
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.60
N. Mahani, Alireaza Mohadesi Zarandi, Azra Horzadeh
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引用次数: 3
Plants used as painkiller in folk medicine in Turkey – III: Rheumatic pain 土耳其民间医药中用作止痛药的植物- III:风湿痛
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.50
Meryem Seyda Erbay, S. Anıl, G. Melikoğlu
There are many plants used by the public in the treatment of various diseases in Turkey.The folk remedies prepared with these plants from which treatment and how they used have been reached to day-to-day by transferring the generations. The traditional treatment methods are recorded by ethnobotanical researches and it is aimed to contribute to drug development studies. In this study, which was prepared by screening of ethnobotanical researches, 72 taxa which used in traditional treatment against rheumatic pain in Turkey are reached and the scientific and local names, families, used parts of these taxa and the use forms in rheumatic pain were compiled. According to the research done, families that are commonly used for rheumatic pain are Ranunculaceae (8 taxa), Asteraceae (5 taxa), Brassicaceae (5 taxa), Lamiaceae (5 taxa), Apiaceae (4 taxa) and Liliaceae (4 taxa). The plants used for rheumatic pain contain analgesic, anti-inflammatory, antiseptic and rubefian compounds. Rubefian compound containing species are applied externally to the rheumatoid region and act by increasing the blood supply of the region. Analgesic, anti-inflammatory and antiseptic active species are used in the form of decoction / infusion both internally and externally.
在土耳其,公众使用许多植物来治疗各种疾病。用这些植物准备的民间偏方,从哪里治疗和如何使用,已经通过代代相传达到了日常。民族植物学研究记录了传统的治疗方法,旨在为药物开发研究做出贡献。本研究通过对民族植物学研究资料的筛选,获得了土耳其传统治疗风湿性疼痛的72个类群,并编制了这些类群的学名和当地名称、科、使用部位以及在风湿性疼痛中的使用形式。根据研究,常用于治疗风湿性疼痛的科有毛茛科(8个分类群)、Asteraceae(5个分类群)、芸苔科(5个分类群)、Lamiaceae(5个分类群)、Apiaceae(4个分类群)和lilaceae(4个分类群)。用于治疗风湿性疼痛的植物含有镇痛、抗炎、抗菌和rubbean化合物。含有种类的rubbean化合物外用于类风湿区域,并通过增加该区域的血液供应而起作用。镇痛、抗炎、杀菌活性物质以汤剂/输注形式内服外用。
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引用次数: 4
Evaluation of anti-proliferative and cytotoxic effects of chlorogenic acid on breast cancer cell lines by real-time, label-free and high-throughput screening 实时、无标记和高通量筛选评价绿原酸对乳腺癌细胞系的抗增殖和细胞毒作用
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.54
O. Bender, A. Atalay
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引用次数: 16
Potential protective effects of silk fibroin against ethanol induced gastric ulcer 丝素蛋白对乙醇性胃溃疡的潜在保护作用
Pub Date : 2018-04-06 DOI: 10.12991/mpj.2018.53
A. Aykaç, Buse Karanlik, A. Sehirli
ABSTRACT: Ulcers that develop due to alcohol consumption are frequently confronted. The aim of this study was to investigate the protective effects of silk fibroin on the pro-apoptotic and anti-apoptotic protein expression levels on ethanol induced-ulcer models in rats. For three consecutive days, orogastrically either silk fibroin or saline were given to rats. On the 4th day, animals were deprived of food but allowed free access to water for 24 h before the experiment. While control groups were treated with only physiological saline, the ulcer groups were treated orally either with saline or silk fibroin groups. For ulcer induction, 1 ml of absolute ethanol by gavage were given to both group. Firstly, intracardiac blood was taken at 60 min of EtOH or saline administration and immediately animals were decapitated. In blood samples, the amount of TNF-, IL-1β were analysed whereas in stomach tissues, the levels of MDA, GSH, and MPO activity and the expression levels of bcl-2, Bax, caspase-3 and -9 were determined. In ulcer groups, the amount of TNF- , IL-1β, MDA, MPO, caspase-3 and caspase-9 were found to be significantly higher compared to control groups whereas in GSH, Bcl-2/Bax were found to be lower (p < 0.005). In treatment groups it is observed that silk fibroin recovers the amount of TNF-, IL 1-β, MDA, MPO, GSH, caspase-3, caspase-9, and Bcl2/Bax. In conclusion, for the treatment of the gastric ulcer SF thought to be very efficient therapeutic agent.
摘要:酒精引起的溃疡是常见的问题。本研究旨在探讨丝素蛋白对乙醇性溃疡模型大鼠促凋亡和抗凋亡蛋白表达水平的保护作用。给大鼠连续3天口服丝素或生理盐水。第4天,实验前24 h不给食物,自由饮水。对照组只给予生理盐水治疗,溃疡组给予生理盐水或丝素素口服治疗。两组均灌胃无水乙醇1 ml诱导溃疡。首先,在EtOH或生理盐水给药60分钟时取心内血,立即将动物斩首。在血液样本中,分析TNF-,IL-1β的量,而在胃组织中,测定MDA, GSH和MPO活性水平以及bcl-2, Bax, caspase-3和-9的表达水平。溃疡组TNF-、IL-1β、MDA、MPO、caspase-3、caspase-9含量显著高于对照组,而GSH、Bcl-2/Bax含量显著低于对照组(p < 0.005)。在治疗组中,观察到丝素蛋白恢复了TNF-、IL 1-β、MDA、MPO、GSH、caspase-3、caspase-9和Bcl2/Bax的量。综上所述,SF被认为是治疗胃溃疡非常有效的治疗剂。
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引用次数: 2
Ethnobotanical usage of plants as aphrodisiac agents in Anatolian folk medicine 安纳托利亚民间医学中用作壮阳剂的植物的民族植物学用途
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.51
Selin Tufan, G. G. Toplan, A. Mat
Several plants have been used as aphrodisiac to treat sexual problems for centuries. Nowadays, despite the synthesis of chemicals, herbal medicines continue to maintain their importance. Turkey has a great tradition of folk medicine due to its rich flora and many plants have been used for the treatment of several disorders. This work presents aphrodisiac plants traditionally used in Turkey, with their local names, used parts, usage and administration route.
几个世纪以来,有几种植物一直被用作壮阳药来治疗性问题。如今,尽管化学物质的合成,草药继续保持其重要性。由于其丰富的植物群和许多植物被用于治疗几种疾病,土耳其有一个伟大的民间医学传统。这项工作介绍了土耳其传统上使用的催情植物,以及它们的当地名称,使用部位,用法和管理路线。
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引用次数: 3
Social isolation and predator scent tests alter brain BDNF levels differentially according to gender, in rats and effects of fluoxetine 社会隔离和捕食者气味测试会根据性别、老鼠和氟西汀的影响改变大脑BDNF水平
Pub Date : 2018-04-06 DOI: 10.12991/MPJ.2018.56
A. Aykaç, Şule Öncül, R. Onur
We compared different stress conditions on brain BDNF levels, in rats exposed to social isolation test (SIT) and predator scent tests (PST). BDNF expression in the frontal cortex, hippocampus, and amygdala was compared, and effects of chronic fluoxetine (FLU) treatment were evaluated. Rats were exposed to SIT and PST for one month. FLU was given (5 mg/kg/day, ip) throughout stress procedures. Controls, stress, and treatment groups were evaluated in elevated plus maze, anxiety scores were calculated. BDNF expression was determined by Western blot. SIT and PST induced anxiety in both sexes, females had greater anxiety scores than males (p<0.05). FLU restored anxiety scores in both sexes (p<0.01) in both tests. Male and female rats exhibited reduced cortical BDNF levels in SIT (p<0.001). PST reduced cortical BDNF in females, but increased in males. Hippocampal BDNF expression was lowered in SIT (p<0.01) and PST (p<0.001) in both sexes. Female rats had 40% lower BDNF expression than males in the amygdala in SIT. FLU did not restore cortical BDNF in females in both tests, but reduced increased BDNF levels in males in PST (p<0.001). FLU did not restore reduced brain BDNF in males in the hippocampus and amygdala, but restored in hippocampus, in females. Our findings indicate that sex differences must be considered in studies related to mood disorders of animal models, and suggest that BDNF expression in different brain regions are altered differentially in a gender-dependent manner in rats. Antianxiety effect of FLU is not mediated through increasing BDNF activity in cortex in both genders. Increased BDNF in hippocampus and amygdala may reflect antidepressant effect of FLU in female rats, but not in males.
我们比较了暴露于社会隔离测试(SIT)和捕食者气味测试(PST)的大鼠在不同应激条件下脑BDNF水平的变化。比较额叶皮质、海马和杏仁核中BDNF的表达,并评估慢性氟西汀(FLU)治疗的效果。大鼠暴露于SIT和PST一个月。在整个应激过程中给予流感(5mg /kg/天,ip)。对照组、应激组和治疗组在升高加迷宫中进行评估,计算焦虑评分。Western blot检测BDNF表达。SIT和PST诱导男女焦虑,女性焦虑得分高于男性(p<0.05)。在两项测试中,流感恢复了两性的焦虑得分(p<0.01)。雄性和雌性大鼠在SIT中表现出皮层BDNF水平降低(p<0.001)。PST在女性中降低皮质BDNF,但在男性中增加。海马BDNF表达在SIT组(p<0.01)和PST组(p<0.001)均明显降低。雌性大鼠的扁桃体BDNF表达比雄性大鼠低40%。在两项试验中,流感均未恢复女性皮质BDNF,但降低了PST患者男性皮质BDNF水平的升高(p<0.001)。流感没有恢复雄性海马和杏仁核中减少的脑BDNF,但在雌性海马中恢复。我们的研究结果表明,在与动物模型情绪障碍相关的研究中必须考虑性别差异,并表明大鼠脑不同区域的BDNF表达以性别依赖的方式发生差异。在两性中,流感的抗焦虑作用不是通过增加皮质BDNF活性介导的。雌性大鼠海马和杏仁核BDNF的增加可能反映了流感的抗抑郁作用,而雄性大鼠则没有。
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引用次数: 1
期刊
Marmara Pharmaceutical Journal
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