• 【合成一些新的喹喔啉和1,2,4-三唑并[4,3-a]-喹喔啉以评估体外抗肿瘤和抗菌活性。】 复制标题 收藏 收藏
    DOI:10.1002/ardp.200600061 复制DOI
    作者列表:El-Hawash SA,Habib NS,Kassem MA
    BACKGROUND & AIMS: :Two novel series of quinoxalines derived from 3-phenylquinoxalin-2(1H)-one and 2-hydrazino-3-phenylquinoxaline, namely 1-substituted-3-phenylquinoxaline-2(1H)-ones, 2a-c, 3a-d, and 4; 2-(3-oxo-3,3a,4,5,6,7-hexahydroindazol-2-yl)-3-phenylquinoxaline 6; N- cyclopentylidene or benzylidene-N'-(3-phenylquinoxaline-2-yl)hydrazines, 7 and 18; 1-substituted-4-phenyl-1,2,4-triazolo[4,3-a]quinoxalines, 9, 10, 12, 13, 14, and 16 have been synthesized in order to evaluate their antitumor and antimicrobial activities. Preliminary screening at NCI showed that compounds 2b, 2c, 3b, 3c, and 9 exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10(-6) to 10(-5) molar concentrations. Compound 3b was the most active with a broad spectrum of activity. Compound 3c showed selectivity towards CNS-cancer SF-639, leukemia CCRF-CEM, and melanoma SK-MEL-5 (GI(50) = 4.03, 6.46, and 4.17 microM, respectively). On the other hand, the in vitro microbiological data revealed that the prepared compounds showed mild antimicrobial activity.
    背景与目标: :由3-苯基喹喔啉-2(1H)-one和2-肼基-3-苯基喹喔啉衍生的两个新颖的喹喔啉系列,即1-取代-3-苯基喹喔啉-2(1H)-ones,2a-c,3a-d ,和4; 2-(3-氧代-3,3a,4,5,6,7-六氢吲唑-2-基)-3-苯基喹喔啉6; N-环戊叉基或亚苄基-N'-(3-苯基喹喔啉-2-基)肼,7和18;为了评估它们的抗肿瘤和抗菌活性,已经合成了1-取代的4-苯基-1,2,4-三唑并[4,3-a]喹喔啉,9、10、12、13、14和16。在NCI上进行的初步筛选显示,化合物2b,2c,3b,3c和9对摩尔浓度在10(-6)至10(-5)之间的各种肿瘤细胞系表现出中等至强的生长抑制活性。化合物3b是最活跃的,具有广泛的活性。化合物3c显示出对CNS癌症SF-639,白血病CCRF-CEM和黑色素瘤SK-MEL-5的选择性(分别为GI(50)= 4.03、6.46和4.17 microM)。另一方面,体外微生物学数据显示所制备的化合物显示出温和的抗微生物活性。
  • 【抗惊厥剂直接抑制类固醇生成细胞色素P-450单加氧酶系统的活性。】 复制标题 收藏 收藏
    DOI:10.1016/s0960-0760(96)00166-5 复制DOI
    作者列表:Ohnishi T,Ichikawa Y
    BACKGROUND & AIMS: :The effects of anticonvulsants on the activities of cytochromes P-450(17alpha,lyase) (CYP17), P-450arom (CYP19), P-450C21 (CYP21), P-450SCC (CYP11A1), and P-450(11beta) (CYP11B1) mono-oxygenase systems were studied using rat testicular microsomes, human placental microsomes, bovine adrenocortical microsomes, bovine adrenocortical mitochondria and purified cytochrome P-450(11beta). Phenytoin, clonazepam and carbamazepine inhibited the steroidogenesis catalysed by these cytochrome P-450 mono-oxygenase systems and the Ki values for each anticonvulsant were determined. Neither hydantoin nor sodium valproate inhibited the activities of steroidogenic cytochromes P-450. When the activities of cytochromes P-450arom and P-450C21 were measured in the presence of anticonvulsants, the Ki values (0.15 mM) for phenytoin were close to the plasma concentration of phenytoin under therapeutic conditions. Phenytoin, clonazepam and carbamazepine directly inhibited the monooxygenase activities of cytochromes P-450, because they did not affect the activities of NADPH-cytochrome P-450 reductase, NADPH-adrenoferredoxin reductase and adrenoferredoxin.
    背景与目标: :抗惊厥药对细胞色素P-450(17α,裂解酶)(CYP17),P-450arom(CYP19),P-450C21(CYP21),P-450SCC(CYP11A1)和P-450(11beta)活性的影响(CYP11B1)单加氧酶系统使用大鼠睾丸微粒体,人胎盘微粒体,牛肾上腺皮质微粒体,牛肾上腺皮质线粒体和纯化的细胞色素P-450(11beta)进行了研究。苯妥英钠,氯硝西am和卡马西平抑制了这些细胞色素P-450单加氧酶系统催化的类固醇生成,并确定了每种抗惊厥药的Ki值。乙内酰脲或丙戊酸钠均不抑制类固醇生成细胞色素P-450的活性。当在抗惊厥药存在下测量细胞色素P-450arom和P-450C21的活性时,苯妥英的Ki值(0.15 mM)接近于治疗条件下苯妥英的血浆浓度。苯妥英钠,氯硝西am和卡马西平直接抑制细胞色素P-450的单加氧酶活性,因为它们不影响NADPH-细胞色素P-450还原酶,NADPH-肾上腺铁氧还蛋白还原酶和肾上腺铁氧还蛋白的活性。
  • 【台湾地区替加环素与其他抗微生物剂对肺炎链球菌,流感嗜血杆菌和卡他莫拉菌的体外活性比较。】 复制标题 收藏 收藏
    DOI:10.1089/mdr.2006.12.130 复制DOI
    作者列表:Lau YJ,Hsueh PR,Liu YC,Shyr JM,Huang WK,Teng LJ,Liu CY,Luh KT
    BACKGROUND & AIMS: :We compared the in vitro activities of tigecycline to those of other agents against 300 nonduplicate isolates of Streptococcus pneumoniae (194 isolates), Haemophilus influenzae (60 isolates), and Moraxella catarrhalis (46 isolates) recovered from patients treated in three major hospitals in Taiwan from August through December, 2003. All of these isolates were inhibited at 0.5 mg/L of tigecycline. For S. pneumoniae isolates, 72% were not susceptible to penicillin (69% intermediate and 3% resistant) and 96% were not susceptible to azithromycin. Among the 178 isolates resistant to azithromycin, 53 isolates (30%) had the M phenotype and 70% had the cMLSB phenotype. The rate of nonsusceptibility to ertapenem, telithromycin, moxifloxacin, and quinupristindalfopristin in S. pneumoniae was 3%, 2%, 1%, and 57%, respectively. For H. influenzae, 36 (60%) were not susceptible to ampicillin, among which 31 possessed beta-lactamase. A high rate (8.3%) of H. influenzae isolates with beta-lactamase-negative and ampicillin-resistant phenotype was found. All H. influenzae isolates were susceptible to azithromycin, but 40% of them were not susceptible to clarithromycin. Ninety-eight percent (44 isolates) of M. catarrhalis possessed beta-lactamase. All three fluoroquinolones tested were highly active (MIC90 < or =0.12 mg/L) against H. influenzae and M. catarrhalis.
    背景与目标: :我们比较了替加环素与其他药物对300株肺炎链球菌(194株),流感嗜血杆菌(60株)和卡他莫拉氏菌(46株)的非重复分离株的体外活性,这些菌株从台湾三家主要医院接受治疗的患者中恢复从2003年8月到2003年12月。所有这些分离株的替加环素浓度为0.5 mg / L。对于肺炎链球菌分离株,72%对青霉素不敏感(69%中度耐药,3%耐药),96%对阿奇霉素不敏感。在对阿奇霉素有抗药性的178株菌株中,有53株(占30%)具有M表型,而70%则具有cMLSB表型。肺炎链球菌对厄他培南,泰利霉素,莫西沙星和奎奴帕辛达福普汀的不敏感率分别为3%,2%,1%和57%。对于流感嗜血杆菌,有36名(60%)对氨苄西林不敏感,其中31名具有β-内酰胺酶。发现高比例(8.3%)的带有β-内酰胺酶阴性和氨苄青霉素抗性表型的流感嗜血杆菌分离株。所有流感嗜血杆菌分离株均对阿奇霉素敏感,但其中40%对克拉霉素不敏感。卡他氏菌的百分之九十八(44个分离株)拥有β-内酰胺酶。测试的所有三种氟喹诺酮类药物对流感嗜血杆菌和卡他莫拉氏菌均具有很高的活性(MIC90 <或= 0.12 mg / L)。
  • 【缺碘雌性大鼠甲状腺和组织中的脱碘酶活性。】 复制标题 收藏 收藏
    DOI:10.1210/en.2012-1727 复制DOI
    作者列表:Lavado-Autric R,Calvo RM,de Mena RM,de Escobar GM,Obregon MJ
    BACKGROUND & AIMS: :Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T(3), and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3) concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4) decreased more than T(3) (50%). The highest type 1 iodothyronine deiodinase (D1) activities were found in the thyroid, kidney, and the liver; pituitary, lung, and ovary had lower D1 activities; but the lowest levels were found in the heart and skeletal muscle. D1 activity decreased in all tissues of LID rats (10-40% of LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold. Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid, brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats and about 20-fold in the whole gland. D2 always increased in response to LID, and maximal increases were found in the cerebral cortex (19-fold), thyroid, brown adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression in other tissues. Our data indicate that LID induces changes in deiodinase activities, especially in the thyroid, to counteract the low T(4) synthesis and secretion, contributing to maintain the local T(3) concentrations in the tissues with D2 activity.
    背景与目标: :严重的碘缺乏症的特征是甲状腺肿大,甲状腺的优先合成和分泌T(3),血浆和组织中的甲状腺素低血症,血浆T(3)正常或较低以及血浆TSH略有增加。我们研究了低碘饮食(LIDs)或补充碘的LID(LID I)维持的大鼠几个组织中脱碘酶活性和mRNA的变化。在LID大鼠的血浆,组织和甲状腺中,T(4)和T(3)的浓度降低,而T(4)的降低幅度大于T(3)(50%)。在甲状腺,肾脏和肝脏中发现最高的1型碘甲状腺素脱碘酶(D1)活性。垂体,肺和卵巢的D1活性较低;但是最低的水平是在心脏和骨骼肌中发现的。除卵巢和甲状腺外,LID大鼠所有组织中的D1活性均降低(LID I大鼠的10-40%),D1活性提高了2.5倍。在甲状腺,褐色脂肪组织和垂体中发现最大的2型碘甲状腺素脱碘酶(D2)活性,在LID大鼠的甲状腺中增加了6.5倍,在整个腺体中增加了约20倍。 D2总是响应LID而增加,在大脑皮层(19倍),甲状腺,褐色脂肪组织和垂体(6倍)中发现最大的增加。在卵巢,心脏和肾上腺中发现较低的D2活性,而LID升高。无法检测到3型碘甲状腺素脱碘酶活性。 LID大鼠的甲状腺Dio1和Dio2 mRNA增加,而肺中Dio1减少,其他组织的mRNA表达没有变化。我们的数据表明,LID诱导脱碘酶活性的变化,尤其是在甲状腺中,以抵消低T(4)的合成和分泌,从而有助于维持具有D2活性的组织中的局部T(3)浓度。
  • 【行为不全的大鼠下牙槽神经横断后三叉神经节和丘脑神经元活动的长期变化。】 复制标题 收藏 收藏
    DOI:10.1523/JNEUROSCI.1828-12.2012 复制DOI
    作者列表:Tseng WT,Tsai ML,Iwata K,Yen CT
    BACKGROUND & AIMS: :The transection of the inferior alveolar nerve (IANx) produces allodynia in the whisker pad (V2 division) of rats. Ectopic discharges from injured trigeminal ganglion (TG) neurons and thalamocortical reorganization are possible contributors to the sensitization of uninjured V2 primary and CNS neurons. To test which factor is more important, TG and ventroposterior medial nucleus (VPM) neurons were longitudinally followed before, during, and after IANx for up to 80 d. Spontaneous discharges and mechanical stimulation-evoked responses were recorded in conscious and in anesthetized states. Results show (1) a sequential increase in spontaneous activities, first in the injured TG neurons of the IAN (2-30 d), followed by uninjured V2 ganglion neurons (6-30 d), and then VPM V2 neurons (7-30 d) after IANx; (2) ectopic discharges included burst and regular firing patterns in the IAN and V2 branches of the TG neurons; and (3) the receptive field expanded, the modality shifted, and long-lasting after-discharges occurred only in VPM V2 neurons. All of these changes appeared in the late or maintenance phase (7-30 d) and disappeared during the recovery phase (40-60 d). These observations suggest that ectopic barrages in the injured IAN contribute more to the development of sensitization, whereas the modality shift and evoked after-discharges in the VPM thalamic neurons contribute more to the maintenance phase of allodynia by redirecting tactile information to the cortex as nociceptive.
    背景与目标: :下牙槽神经(IANx)横断会在大鼠的晶须垫(V2分区)中产生异常性疼痛。受损的三叉神经节(TG)神经元的异位放电和丘脑皮质重组可能是未受伤的V2原发神经元和CNS神经元致敏的原因。为了测试哪个因素更重要,在IANx之前,期间和之后,纵向追踪TG和后内侧内侧核(VPM)神经元长达80 d。在有意识和麻醉状态下记录自发放电和机械刺激诱发的反应。结果显示(1)自发活动依次增加,首先在IAN受伤的TG神经元中(2-30 d),其次是未受伤的V2神经节神经元(6-30 d),然后是VPM V2神经元(7-30) d)在IANx之后; (2)异位放电包括TG神经元IAN和V2分支的爆发和规则放电模式; (3)仅在VPM V2神经元中,感受野扩大,模态改变且持续放电。所有这些变化都出现在后期或维护阶段(7-30 d),而在恢复阶段(40-60 d)则消失了。这些观察结果表明,受伤的IAN的异位弹幕对致敏作用的贡献更大,而VPM丘脑神经元的形态改变和诱发的放电后,则通过将触觉信息重定向至伤害性皮层,从而对异常性疼痛的维持阶段做出了更大贡献。
  • 【烟粉虱烟粉虱的通管针渗透活动与接种crinicvirus番茄萎绿病病毒有关。】 复制标题 收藏 收藏
    DOI:10.1099/jgv.0.000783 复制DOI
    作者列表:Prado Maluta NK,Garzo E,Moreno A,Navas-Castillo J,Fiallo-Olivé E,Spotti Lopes JR,Fereres A
    BACKGROUND & AIMS: :Bemisiatabaci is an important vector of numerous plant viruses, including the emergent semi-persistently transmitted crinivirus Tomato chlorosis virus (ToCV). Its vector feeding behaviour is complex, with important implications for virus transmission, epidemiology and control. Thus, the objective of this study was to investigate the role of the stylet penetration activities of B. tabaci in the inoculation of ToCV in tomatoes by using the electrical penetration graph (EPG) technique. EPG recordings were classified into six categories depending on the waveforms observed. The results showed that ToCV inoculation is mainly associated with stylet activities in phloem sieve elements (E1 waveform), as there was a significant increase in the rate of transmission when whiteflies performed waveform E1. The precise stylet activities - either salivation or egestion - associated with virion release, presumably from retention sites in the foregut, need further investigation.
    背景与目标: 念珠菌是许多植物病毒的重要载体,包括新兴的半持续性传播的crinivirus番茄萎黄病毒(ToCV)。它的媒介摄食行为很复杂,对病毒传播,流行病学和控制具有重要意义。因此,本研究的目的是通过使用电渗透图(EPG)技术研究烟粉虱的探针通透活性在番茄ToCV接种中的作用。 EPG记录根据观察到的波形分为六类。结果表明,ToCV接种主要与韧皮部筛网元素中的探针运动相关(E1波形),因为当粉虱执行波形E1时,传播速率显着增加。与病毒体释放相关的精确的探针活动(唾液分泌或排卵),大概是从前肠的保留位点释放出来的,需要进一步研究。
  • 【Badula barthesia和Embelia angustifolia中苯醌的生物活性。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(98)80028-7 复制DOI
    作者列表:Lund AK,Adsersen A,Nyman U
    BACKGROUND & AIMS: :In our screening program for antihypertensive plant constituents extracts of the leaves and bark of Badula barthesia showed strong in vitro inhibition of angiotensin converting enzyme (ACE). Rapanone (1), 2,5-dihydroxy-3-tridecyl-1,4-benzoquinone, was isolated as an active constituent of the leaves. The IC(50) values of rapanone and three 3-alkyl-2,5-dihydroxybenzoquinones, (2)-(4), (Z)-2,5-dihydroxy-3-(pentadec-8-enyl)-1,4-benzoquinone, (Z,Z)-2,5-dihydroxy-3-(heptadeca-8,11-dienyl)-1,4-benzoqui-none and (Z)-2,5-dihydroxy-3-(heptadec-8-enyl)-1,4-benzoquinone recently isolated from Embelia angustifolia were determined. The following IC(50) ± S.D. values have been obtained (1) 36 ± 4.6 μM, (2) 19 ± 6.2 μM, (3) 19 ± 8.7 μM and (4) 16 ± 3.0 μ.M. The IC(50) value for the reference compound Captopril was determined to 12 ± 2.6 nM. The antimicrobial activity of the four compounds was determined by thin layer chromatography agar overlay technique as minimum growth inhibitory amount in μg. One yeast, Candida albicans, and four bacteria, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus were used as test organisms.
    背景与目标: :在我们针对降压植物成分的筛选程序中,Badula barthesia的叶子和树皮提取物显示出对血管紧张素转化酶(ACE)的强烈抑制作用。分离出2,5-二羟基-3-十三烷基-1,4-苯醌的雷帕酮(1)作为叶片的活性成分。雷帕酮和三个3-烷基-2,5-二羟基苯醌,(2)-(4),(Z)-2,5-二羟基-3-(pentadec-8-enyl)-1, 4-苯醌,(Z,Z)-2,5-二羟基-3-(十七烷基-8,11-二烯基)-1,4-苯并喹酮和(Z)-2,5-二羟基-3-(十七烷基)确定了最近从安哥拉花(Embelia angustifolia)分离的-8-烯基)-1,4-苯醌。以下IC(50)±S.D.已获得(1)36±4.6μM,(2)19±6.2μM,(3)19±8.7μM和(4)16±3.0μM。参考化合物卡托普利的IC(50)值确定为12±2.6 nM。通过薄层层析琼脂覆盖技术确定这四种化合物的抗微生物活性,以μg为单位的最小生长抑制量。将一种酵母,白色念珠菌和四种细菌,枯草芽孢杆菌,大肠杆菌,铜绿假单胞菌和金黄色葡萄球菌用作测试生物。
  • 【在客户直接护理期间的临床讲师的教学活动:定性调查。】 复制标题 收藏 收藏
    DOI:10.1111/j.1365-2648.1991.tb01534.x 复制DOI
    作者列表:Morgan SA
    BACKGROUND & AIMS: :The lack of substantial research in the area of clinical teaching would suggest that this 'heart' of the nursing student's professional education has long been neglected. Employing a qualitative descriptive methodology, this study explored the teaching activities that nine clinical instructors said they implemented during the direct client care period and the teaching activities that these nine clinical instructors said they would implement in response to a specific scenario of a clinical teaching event. The unstructured interviews revealed that clinical instructors: (a) noted role modelling the greatest number of times as a teaching activity but implemented it less frequently; (b) used verbalizations in the form of telling, asking, saying, discussing or talking as the primary teaching activity in the clinical area and in response to the specific scenario; (c) do not have opportunities to see other clinical instructors teaching in the clinical area; (d) have difficulty separating teaching activities and evaluation activities; (e) are eclectic in their use of learning theories; and (f) find articulating teaching activities that they implement during the direct client care period to be a complex task.
    背景与目标: :在临床教学领域缺乏大量研究表明,护理学生的专业教育的“心脏”长期以来一直被忽略。本研究采用定性描述方法,探讨了九位临床指导员表示他们在直接就诊护理期间实施的教学活动,以及这九位临床指导员表示将针对临床教学事件的特定情况而实施的教学活动。非结构化的访谈表明,临床讲师:(a)注意到作为教学活动的榜样次数最多,但实施频率较低; (b)以讲,问,说,讨论或说话的形式进行口头表达,将其作为临床领域的主要教学活动,并根据具体情况做出反应; (c)没有机会去看临床领域的其他临床指导老师的教学; (d)难以将教学活动和评估活动分开; (e)在运用学习理论方面不拘一格; (f)发现他们在直接的客户护理期间实施的清晰的教学活动是一项复杂的任务。
  • 【在日常活动中测量姿势和运动时,新型活动监视器的验证。】 复制标题 收藏 收藏
    DOI:10.1136/bjsm.2006.030262 复制DOI
    作者列表:Grant PM,Ryan CG,Tigbe WW,Granat MH
    BACKGROUND & AIMS: BACKGROUND:Accurate measurement of physical activity patterns can be used to identify sedentary behaviour and may facilitate interventions aimed at reducing inactivity. OBJECTIVE:To evaluate the activPAL physical activity monitor as a measure of posture and motion in everyday activities using observational analysis as the criterion standard. METHODS:Wearing three activPAL monitors, 10 healthy participants performed a range of randomly assigned everyday tasks incorporating walking, standing and sitting. Each trial was captured on a digital camera and the recordings were synchronised with the activPAL. The time spent in different postures was visually classified and this was compared with the activPAL output. RESULTS:Intraclass correlation coefficients (ICC 2,1) for interdevice reliability ranged from 0.79 to 0.99. Using the Bland and Altman method, the mean percentage difference between the activPAL monitor and observation for total time spent sitting was 0.19% (limits of agreement -0.68% to 1.06%) and for total time spent upright was -0.27% (limits of agreement -1.38% to 0.84%). The mean difference for total time spent standing was 1.4% (limits of agreement -6.2% to 9.1%) and for total time spent walking was -2.0% (limits of agreement -16.1% to 12.1%). A second-by-second analysis between observer and monitor found an overall agreement of 95.9%. CONCLUSION:The activPAL activity monitor is a valid and reliable measure of posture and motion during everyday physical activities.
    背景与目标: 背景:对身体活动模式的准确测量可用于识别久坐行为,并可促进旨在减少运动量的干预措施。
    目的:以观察性分析为标准,评估activPAL身体活动监测器,以衡量其日常活动中的姿势和运动。
    方法:10名健康参与者戴着三副activPAL监视器,执行了一系列随机分配的日常任务,包括步行,站立和坐下。每个试验都在数码相机上捕获,并且记录与activPAL同步。用视觉对在不同姿势下花费的时间进行分类,并将其与activPAL输出进行比较。
    结果:设备间可靠性的类内相关系数(ICC 2,1)范围为0.79至0.99。使用Bland和Altman方法,ActivPAL监控器与观察值之间的平均差额为总坐下时间为0.19%(协议限制-0.68%至1.06%),而整个直立时间为-0.27%(协议限制) -1.38%至0.84%)。站立总花费时间的平均差异为1.4%(同意限制-6.2%至9.1%),步行花费总时间的平均差异为-2.0%(同意限制-16.1%至12.1%)。观察者和监测者之间进行的第二次分析发现,总体符合率为95.9%。
    结论:activPAL活动监测器是对日常体育活动中姿势和运动的有效且可靠的测量。
  • 【α-硫辛酸抑制糖尿病大鼠的P2X受体活性和内脏对结直肠扩张的超敏性。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-04283-7 复制DOI
    作者列表:Hu J,Qin X,Song ZY,Yang PP,Feng Y,Sun Q,Xu GY,Zhang HH
    BACKGROUND & AIMS: :The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ATP-induced current density of colon-specific DRG (T13-L2 DRGs) neurons was measured with whole-cell patch clamp. The expression of P2X3Rs of T13-L2 DRGs was measured by western blot analysis. The results showed that AWR scores significantly increased after STZ injection. P2X3R expression and ATP current density of T13-L2 DRG neurons were enhanced in diabetic rats. Intraperitoneal injection with ALA once a day for 1 week remarkably reduced P2X3R expression and ATP current density in diabetic rats. Importantly, ALA treatment attenuated colonic hypersensitivity in diabetic rats. Our data suggest that STZ injection increases expression and function of P2X3 receptors of colon-specific DRG neurons, thus contributing to colonic hypersensitivity in diabetic rats. Administration of ALA attenuates diabetic colonic hypersensitivity, which is most likely mediated by suppressing expression and function of P2X3 receptors in DRGs of diabetic rats.
    背景与目标: :本研究旨在研究背根神经节(DRG)神经元中P2X3受体在结肠超敏中的作用以及α-硫辛酸(ALA)对糖尿病大鼠P2X3受体活性和结肠超敏性的影响。链脲佐菌素(STZ)用于诱导糖尿病模型。记录对结肠扩张(CRD)的腹部缩回反射(AWR)作为结肠敏感性。用全细胞膜片钳测量ATP诱导的结肠特异性DRG(T13-L2 DRGs)神经元的电流密度。通过蛋白质印迹分析测量T13-L2 DRG的P2X3R的表达。结果表明,注射STZ后AWR分数显着增加。 T13-L2 DRG神经元的P2X3R表达和ATP电流密度在糖尿病大鼠中增强。每天一次腹膜内注射ALA,持续1周,可显着降低糖尿病大鼠的P2X3R表达和ATP电流密度。重要的是,ALA治疗可减轻糖尿病大鼠的结肠超敏反应。我们的数据表明,STZ注射可增加结肠特异性DRG神经元的P2X3受体的表达和功能,从而促进糖尿病大鼠的结肠超敏反应。 ALA的给药减弱了糖尿病结肠的超敏反应,这很可能是通过抑制糖尿病大鼠DRG中P2X3受体的表达和功能来介导的。
  • 【线粒体:氧化还原活动和细胞窘迫控制的枢纽。】 复制标题 收藏 收藏
    DOI:10.1007/s11010-007-9520-8 复制DOI
    作者列表:Kakkar P,Singh BK
    BACKGROUND & AIMS: :In their reductionist approach in unraveling phenomena inside the cell, scientists in recent times have focused attention to mitochondria. An organelle with peculiar evolutionary history and organization, it is turning out to be an important cell survival switch. Besides controlling bioenergetics of a cell it also has its own genetic machinery which codes 37 genes. It is a major source of generation of reactive oxygen species, acts as a safety device against toxic increases of cytosolic Ca2+ and its membrane permeability transition is a critical control point in cell death. Redox status of mitochondria is important in combating oxidative stress and maintaining membrane permeability. Importance of mitochondria in deciding the response of cell to multiplicity of physiological and genetic stresses, inter-organelle communication, and ultimate cell survival is constantly being unraveled and discussed in this review. Mitochondrial events involved in apoptosis and necrotic cell death, such as activation of Bcl-2 family proteins, formation of permeability transition pore, release of cytochrome c and apoptosis inducing factors, activation of caspase cascade, and ultimate cell death is the focus of attention not only for cell biologists, but also for toxicologists in unraveling stress responses. Mutations caused by ROS to mitochondrial DNA, its inability to repair it completely and creation of a vicious cycle of mutations along with role of Bcl-2 family genes and proteins has been implicated in many diseases where mitochondrial dysfunctions play a key role. New therapeutic approaches toward targeting low molecular weight compounds to mitochondria, including antioxidants is a step toward nipping the stress in the bud.
    背景与目标: :最近,科学家们以还原论的方法揭示了细胞内部的现象,将注意力集中在线粒体上。具有独特的进化历史和组织的细胞器,事实证明它是重要的细胞存活开关。除了控制细胞的生物能,它还具有自己的遗传机制,可编码37个基因。它是产生活性氧的主要来源,是防止细胞溶质Ca2毒性增加的安全装置,其膜通透性转变是细胞死亡的关键控制点。线粒体的氧化还原状态在抵抗氧化应激和维持膜通透性方面很重要。在决定细胞对多种生理和遗传压力,细胞间通讯以及最终细胞存活的反应中,线粒体的重要性正在不断地被探讨和讨论。涉及凋亡和坏死细胞死亡的线粒体事件,例如Bcl-2家族蛋白的激活,通透性过渡孔的形成,细胞色素c和凋亡诱导因子的释放,胱天蛋白酶级联的激活以及最终细胞死亡等,不是人们关注的焦点。不仅适用于细胞生物学家,还适用于毒理学家,以阐明压力反应。 ROS引起的线粒体DNA突变,其无法完全修复,突变的恶性循环以及Bcl-2家族基因和蛋白质的作用,在许多疾病中都与线粒体功能障碍起着关键作用。将低分子量化合物靶向线粒体(包括抗氧化剂)的新治疗方法是消除发芽压力的一步。
  • 【Plantagiolides I和J,两个新的来自塔克拉(Tacca plantaginea)的withanolide糖苷,具有核因子-κB抑制和过氧化物酶体增殖物激活的受体反式激活活性。】 复制标题 收藏 收藏
    DOI:10.1248/cpb.c12-00550 复制DOI
    作者列表:Quang TH,Ngan NT,Minh CV,Kiem PV,Yen PH,Tai BH,Nhiem NX,Thao NP,Anh Hle T,Luyen BT,Yang SY,Kim YH
    BACKGROUND & AIMS: :A novel withanolide glucoside, plantagiolide I (1), a new withanolide glucoside, plantagiolide J (2), and six known compounds (3-8) were isolated from the whole plant of Tacca plantaginea. Their structures were determined by spectroscopic and chemical methods. Compound 3 significantly inhibited tumor necrosis factor alpha (TNFα)-induced nuclear factor-kappaB (NF-κB) transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values of 9.0 µM. Compounds 1-8 enhanced the transcriptional activity of peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner, with EC(50) values ranging from 1.6 to 49.7 µM. In addition, the transactivational effects of compounds 1-8 on three individual PPAR subtypes, including PPARα, β(δ), and γ were evaluated. Compounds 1-8 significantly activated the transcriptional activity of PPARβ(δ), with EC(50) values in a ranging from 4.1 to 29.6 µM. These results provide scientific support for the use of T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.
    背景与目标: :从塔克拉(Tacca plantaginea)的整个植物中分离出一种新的withanolide葡糖苷植物plant内酯I(1),一种新的withanolide葡糖苷,plantagiolide J(2)和六种已知化合物(3-8)。通过光谱和化学方法确定它们的结构。化合物3剂量依赖性地显着抑制HepG2细胞中肿瘤坏死因子α(TNFα)诱导的核因子-κB(NF-κB)转录活性,IC(50)值为9.0μM。化合物1-8以剂量依赖的方式增强了过氧化物酶体增殖物激活受体(PPAR)的转录活性,EC(50)值在1.6至49.7µM之间。另外,评价了化合物1-8对三种单独的PPAR亚型,包括PPARα,β(δ)和γ的反式激活作用。化合物1-8显着激活PPARβ(δ)的转录活性,EC(50)值在4.1至29.6µM之间。这些结果为植物假单胞菌及其成分用于炎性和代谢性疾病的预防和治疗提供了科学依据。
  • 【排尿利尿剂的研究。 I.黄嘌呤氧基氧乙酸和二氢呋喃蒽酮-2-羧酸的合成和活性。】 复制标题 收藏 收藏
    DOI:10.1248/cpb.38.1266 复制DOI
    作者列表:Sato H,Dan T,Onuma E,Tanaka H,Koga H
    BACKGROUND & AIMS: :A series of substituted xanthonyloxyacetic acids (5 and 6), 1,2-dihydrofuro[2,3-c]xanthone-2-carboxylic acids (7) and 2,3-dihydrofuro[3,2-b]xanthone-2-carboxylic acids (8) were synthesized and tested for diuretic and uricosuric activities in rats. Most of the xanthon-3-yloxyacetic acids (5) and 7 showed potent diuretic activities, while 8 had lower activities. Uricosuric activities were found in 5c, 5f, 5k, 5m, 5o, 5p, 5r, 7m, 7p and 8q.
    背景与目标: :一系列取代的氧杂蒽氧基氧乙酸(5和6),1,2-二氢呋喃[2,3-c]蒽酮-2-羧酸(7)和2,3-二氢呋喃[3,2-b]蒽酮-2合成了α-羧酸(8)并测试了大鼠的利尿和尿尿排尿活性。多数x吨-3-基氧基乙酸(5)和7显示出强效的利尿活性,而8种则具有较低的利尿活性。在5c,5f,5k,5m,5o,5p,5r,7m,7p和8q中发现了泌尿外科活动。
  • 【苄腺嘌呤对吸收的黑克子叶线粒体活性发展的影响。】 复制标题 收藏 收藏
    DOI:10.1016/S0176-1617(84)80093-0 复制DOI
    作者列表:Morohashi Y
    BACKGROUND & AIMS: :The development of mitochondria was followed in black gram cotyledons cultured on filter paper wetted with water or benzyladenine solution. Treatment with benzyladenine brought about an increase in activities of some mitochondrial enzymes and in respiratory activities of mitochondria. Cycloheximide did not inhibit the increase, although it almost completely inhibited the incorporation of (14)C-leucine into mitochondrial protein. It was inferred that the increase in mitochondrial activity by benzyladenine-treatment was not due to biogenesis of mitochondria but due to an acceleration of activation processes in pre-existing mitochondria. The respiratory control ratio of mitochondria from benzyladenine-treated cotyledons was lower than that of mitochondria from untreated ones. It was also suggested that benzyladenine brought about some qualitative changes in mitochondrial activities.
    背景与目标: :在用水或苄基腺嘌呤溶液润湿的滤纸上培养的黑克子叶中追踪线粒体的发育。用苄基腺嘌呤治疗导致某些线粒体酶活性和线粒体呼吸活性增加。环己酰亚胺没有抑制这种增加,尽管它几乎完全抑制了(14)C-亮氨酸掺入线粒体蛋白中。据推测,通过苄腺嘌呤处理增加的线粒体活性不是由于线粒体的生物发生,而是由于预先存在的线粒体中活化过程的加速。苄腺嘌呤处理的子叶的线粒体呼吸控制率低于未处理的子叶的线粒体呼吸控制率。还建议苄基腺嘌呤在线粒体活性方面带来一些质的变化。
  • 【非洲传统草药中的有丝分裂活动(第二部分)。】 复制标题 收藏 收藏
    DOI:10.1016/S0944-7113(96)80078-X 复制DOI
    作者列表:Tachibana Y,Kato A,Nishiyama Y,Ikemi M,Ohoka K,Kawanishi K,Juma FD,Ngángá JN,Mathenge SG
    BACKGROUND & AIMS: :Mitogenic activities in African traditional herbal medicines were examined on human peripheral blood lymphocytes and mouse spleen cells using protein fractions obtained from their extracts by precipitation with ammonium sulfate. Target specificity for these mitogens was investigated by using isolated T cells and lymphocytes from athymic nude mice. Among 20 plants investigated, potent mitogenic activities for both human and mouse lymphocytes were found in 7 plants: Monanthotaxis sp. (Annonaceae), Uvaria lucida (Annonaceae), Maytenus buchananii (Celastraceae), Lonchocarpus bussei (Leguminosae), Phytolacca dodecandra (Phytolaccaceae), Phytolacca octandra (Phytolaccaceae), and Toddalia asiatica (Rutaceae). The U. lucida stem demonstrated the highest activity among all and induced mitogenesis both in human and mouse isolated T cells, but not in lymphocytes from athymic nude mice.
    背景与目标: :使用硫酸铵沉淀法从其提取物中获得的蛋白质馏分,检查了非洲传统草药对人外周血淋巴细胞和小鼠脾细胞的促有丝分裂活性。通过使用来自无胸腺裸鼠的分离的T细胞和淋巴细胞,研究了这些促分裂原的靶标特异性。在研究的20种植物中,在7种植物中发现了对人和小鼠淋巴细胞均有效的促有丝分裂活性:Monanthotaxis sp。 (Annonaceae),Uluca lucida(Annonaceae),Maytenus buchananii(Celastraceae),Lonchocarpus bussei(Leguminosae),Phytolacca dodecandra(Phytolaccaceae),Phytolacca octandra(Phytolaccaceae)和Toddalia asiatica。在人和小鼠分离的T细胞中,U。lucida茎表现出最高的活性并诱导有丝分裂发生,而无胸腺裸鼠的淋巴细胞则没有。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录