Methylene blue and Alzheimer's disease

The relationship between methylene blue (MB) and Alzheimer's disease (AD) has recently attracted increasing scientific attention since it has been suggested that MB may slow down the progression of this disease. In fact, MB, in addition to its well characterized inhibitory actions on the cGMP pathway, affects numerous cellular and molecular events closely related to the progression of AD. Currently, MB has been shown to attenuate the formations of amyloid plaques and neurofibrillary tangles, and to partially repair impairments in mitochondrial function and cellular metabolism. Furthermore, various neurotransmitter systems (cholinergic, serotonergic and glutamatergic), believed to play important roles in the pathogenesis of AD and other cognitive disorders, are also influenced by MB. Recent studies suggest that the combination of diverse actions of MB on these cellular functions is likely to mediate potential beneficial effects of MB. This has lead to attempts to develop novel MB-based treatment modalities for AD. In this review article, actions of MB on neurotransmitter systems and multiple cellular and molecular targets are summarized with regard to their relevance to AD.     

Methylene blue and the neurotoxic mechanisms of ifosfamide encephalopathy

In cancer chemotherapy with ifosfamide the occurrence of a drug-related encephalopathy represents a severe adverse-effect of unknown origin. We found that the underlying mechanism resides in the mitochondrial toxicity of ifosfamide metabolites. The electron accepting drug methylene blue can substitute for the demonstrated flavoprotein deficiency and its administration leads to resolution of the encephalopathy in patients. The prophylactic administration of methylene blue is equally effective via another principal mechanism, namely oxidation of the excessive quantity of NADH formed during ifosfamide metabolism. The inhibition by methylene blue of multiple amine oxidase activities also prevents formation of the neurotoxic chloroacetaldehyde from ifosfamide-derived chloroethyl amine. Thus, methylene blue exhibits several synergistic modes of actions which enable the dose-limiting neurotoxicity of alkylating chemotherapy with ifosfamide in cancer patients to be overcome Received: 9 October 1995/Accepted in revised form: 30 January 1996     

MB-P对病毒灭活血浆有效成分的影响

目的 探讨亚甲蓝光化学法血浆病毒灭活对血浆有效成分的影响.方法 使用血凝仪对血浆进行Ⅷ活性和纤维蛋白原含量检测 使用分光光度计测定血浆总蛋白浓度的变化.结果 新鲜冰冻血浆经MB-P病毒灭活后血浆Ⅷ因子活性为（0.66±0.06）IU/ml,比灭活前（0.75±0.07）IU/ml降低,纤维蛋白原含量为（1.31±0.1）mg/ml,比灭活前（2.19±0.2）mg/ml减少,两者比较差异均有显著性（P＜0.05）,总蛋白含量比较差异无显著性（P＞0.05）.结论 在制备冷沉淀时,可考虑先将新鲜冰冻血浆制备冷沉淀后再将血浆进行病毒灭活.灭活后血浆对于临床需要补充血浆蛋白的患者影响不大 对于需要输注Ⅷ因子、纤维蛋白原的患者则会有一定影响.     

Toxicological effects of chlorpyrifos on growth,enzyme activity and chlorophyll a synthesis of freshwater microalgae

This paper aims to acquire the experimental data on the eco-toxicological effects of agricultural pollutants on the aquatic plants and the data can support the assessment of toxicity on the phytoplankton. The pesticide of Chlorpyrifos used as a good model to investigate its eco-toxicological effect on the different microalgae in freshwater. In order to address the pollutants derived from forestry and agricultural applications, freshwater microalgae were considered as a good sample to investigate the impact of pesticides such as Chlorpyrifos on aquatic life species. Two microalgae of Chlorella pyrenoidosa and Merismopedia sp. were employed to evaluate toxicity of Chlorpyrifos in short time and long time by means of measuring the growth inhibition rate, the redox system and the content of chlorophyll a, respectively. In this study, the results showed that EC₅₀ values ranging from 7.63 to 19.64 mg/L, indicating the Chlorpyrifos had a relatively limited to the growth of algae during the period of the acute toxicity experiment. Moreover, when two kinds of algae were exposed to a medium level of Chlorpyrifos, SOD and CAT activities were importantly advanced. Therefore, the growth rate and SOD and CAT activities can be highly recommended for the eco-toxicological assessment. In addition, chlorophyll a also could be used as a targeted parameter for assessing the eco-toxicity of Chlorpyrifos on both Chlorella pyrenoidosa and Merismopedia sp.     

亚甲蓝海藻酸微球的研究

报道了一种适合于放大规模的制备多孔隙的海藻酸微球的方法—喷雾-凝聚法。当5％(w／v)海藻酸钠溶液通过3／8″的喷枪在40～60psi气压下喷雾到1mol／L氯化钙溶液中可以形成空隙率最大的微球。亚甲蓝被选作水溶性阳离子模型药物。亚甲蓝的载药方法是吸附法。亚甲蓝的释放度结果表明载药微球在去离子水中释药不完全，在氯化钠溶液中由于钠离子和钙离子的交换使微球崩解而迅速释放药物。结果表明：由喷雾凝聚法制得的海藻酸微球可以作为通过温和的条件载运阳离子药物。     

Acute toxicity assessment of perfluorinated carboxylic acids towards the Baltic microalgae

The presence of high-energy carbon–fluorine bonds in perfluoro compounds lends them great stability and causes them to be environmentally persistent. Relatively little is known about the acute toxicity of perfluorinated carboxylic acids (PFCAs) to ecotoxicological markers such as aquatic plants and animals. This study tested the toxicity of these compounds to the green alga Chlorella vulgaris, the diatom Skeletonema marinoi and the blue-green alga Geitlerinema amphibium, which are species representative of the algal flora of the Baltic Sea. The EC₅₀ values obtained range from 0.28 mM to 12.84 mM. A distinct relationship between hydrophobicity and toxicity is demonstrated. For every extra perfluoromethylene group in the alkyl chain, the toxicity increases twofold. Log EC₅₀ values are very well correlated linearly with both the number of carbon atoms in the perfluoroalkyl chain and the partition coefficients. The results also indicate that there are clear differences between the responses of particular taxonomic groups of algae: blue-green algae and diatoms are far more sensitive to PFCAs than green algae, probably because of differences in cell wall structure.     

亚甲蓝磁性明胶微球的制备及特性试验

目的：制备亚甲蓝磁性明胶微球并检测其特性。方法：采用乳化-交联法制备亚甲蓝磁性明胶微球，高倍镜观察微球粒径大小及形态，紫外-可见分光光度法检测微球中亚甲蓝的含量及其体外释放规律。结果：亚甲蓝磁性明胶微球粒径38—50μm，在4000GS的磁场下动作距离为70—80mm，载药量为9．8％，180min体外累积释放量为90％。结论：亚甲蓝磁性明胶微球是一种新剂型，制备工艺简便，具有较好的磁响应性和一定缓释性。     

Inhibition of growth and photosynthesis of selected green microalgae as tools to evaluate toxicity of dodecylethyldimethyl-ammonium bromide

The effect of dodecylethyldimethyl-ammonium bromide (DEAB), a quaternary ammonium, compound widely used as disinfectant, on phytoplankton of inland water systems was analysed by using an experimental model. A toxicity test was based on inhibition of photosynthesis performances (effective quantum yield from photosystem II, Φ_PSII and O₂ production) of the phytoplanktonic species Scenedesmus intermedius and Dictiosphaerium chlorelloides (Chlorophyceae) under growing doses of DEAB. A concentration-dependent toxic response was obtained in both parameters analysed. In addition, this response was almost immediate. Consequently, the measurement of both parameters (Φ_PSII and O₂ production) allows to assess DEAB toxicity with higher standards of precision and repeatability. We propose that this procedure could be used to detect presence of quaternary ammonium pollutants in freshwater.     

Green and ecofriendly bio-removal of methylene blue dye from aqueous solution using biologically activated banana peel waste

Using of bio-wastes in dye adsorption is one of the greenest influential applied techniques for the removal of dyestuff from the industrial effluents and it considered as waste management. In the current study, banana peel waste (BPW) was used as an inexpensive and eco-friendly adsorbent for methylene blue (MB) dye. Mechanical pretreatment of BPW was carried out and followed by biological activation using Rhizopus microspores. MB dye was adsorbed by mechanically pretreated BPW (mBPW) by 31%. Moreover, the day nine fermented BPW fibers (mbBPW) is the best time for R. microspores to complete activation, where adsorption ratio reached to about 96.5%. Likewise, enzymes activity was recorded the highest activity after this period of fermentation, where enzymes activity of cellulase, xylanase, lignin peroxidase, poly phenol oxidase and laccase were 0.75, 0.68, 0.38, 0.55 and 0.32 U/ml, respectively. The FT-IR, SEM and BET were used to observe the effect of treatment on the BPW. Otherwise, the kinetics study is illustrated that the adsorption of MB with mbBPW fitted with pseudo-first-order kinetic models. However, the adsorption parameters indicated that the Langmuir model is better to describe the adsorption of dye with excellent maximum adsorption capacity 991 mg/g. In conclusion, biologically activated BPW is very efficient for dye adsorption as well as waste management.     

增敏荧光法测定血浆中亚甲蓝含量及其残留量检测

目的 建立检测血浆中微量亚甲蓝的增敏荧光分光光度法.方法 利用β-环糊精对亚甲蓝荧光信号的增敏作用,以665nm为激发波长,680nm为发射波长,用荧光分光光度法直接测定血浆中的微量亚甲蓝.结果 用β-环糊精增敏时,亚甲蓝浓度在0.012~2.283μmol/L范围内呈现良好的线性关系（r=0.9994）,高中低浓度的日内变异系数（CV）分别为0.19%、0.41%和 1.14%,日间CV分别为1.76%、2.24%和2.97%,标准曲线法测得回收率为99.39~102.30%,对照品比较法测得回收率为96.93%~104.02%.结论 本研究体现出了简单,准确、快捷的特点,实现了无需进行分离、富集达到直接测定血浆中亚甲蓝浓度的目的.     

美兰在乳腺导管内乳头状瘤手术中的应用

目的探讨美兰在乳腺导管内乳头状瘤手术中的应用价值。方法回顾性分析我院乳腺导管内乳头状瘤伴乳头血性溢液患者28例手术治疗的临床资料,并结合文献分析。结果28例均行手术治疗,19例经美兰染色后整个区段染色,9例因肿瘤阻塞管腔仅能使区段部分染色,按美兰染色标示完整切除该区段,病理检查结果显示切除边缘无肿瘤残留。随访3年,1例于乳头部复发,经再次手术治愈。结论美兰染色可清楚显示肿瘤区段,便于完成切除肿瘤区段,简便易行,值得推广。     

亚甲蓝对成人感染性休克血流动力学的影响研究

目的研究分析亚甲蓝对成人感染性休克血流动力学的影响。方法选取本院2012年3月～2013年3月收治的86例感染性休克患者的临床资料进行回顾性分析,将其平均分成对照组和观察组,对照组患者按照常规休克的治疗方法进行治疗;观察组患者在此基础上采用亚甲蓝治疗,比较分析两组患者的血流动力学监测指标。结果两组成人感染性休克患者在治疗前后中心静脉压（CVP）、股动脉平均压（MAP）、平均肺动脉压（MPAP）、肺毛细血管楔压（PCWP）、外周血管阻力指数（SVRI）、肺血管阻力指数（PVRI）等各项指标差异有统计学意义（P〈0．05）。两组患者治疗效果比较,差异有统计学意义（P之0．05）。结论亚甲蓝可以明显改善成人感染性休克患者血流动力学异常的情况,有效治愈感染性休克。     

创伤性休克兔血浆一氧化氮的动态变化及亚甲蓝的干预作用

目的 观察创伤性休克兔血浆一氧化氮(nitric oxide,NO)的动态变化及鸟苷酸环化酶抑制药亚甲蓝(Methylene Blue，MB)的干预作用。方法 选用大白兔18只，分为对照组(6只)，生理盐水复苏组(6只)，MB处理组(6只)，生理盐水复苏组及MB处理组记录休克前(T1)、休克末(T2)、复苏末(T3)，复苏后0．5h(T4)、2h(T5)、4h(T6)时间点收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)及心率(HR)的动态变化，并测定血浆NO的水平，对照组记录相应时间点SBP、DBP、MAP及HR的动态变化，并测定血浆NO的水平。结果兔创伤性休克后，血浆NO水平明显高于休克前，生理盐水复苏组动物复苏后血浆NO进行性增高，于复苏后30分钟达峰值水平，以后逐渐下降，但仍高于休克前；MB处理组动物复苏后血浆NO水平明显降低；对照组各时间点血浆NO无明显变化。结论NO在创伤性休克的病理发展过程中起着重要作用，应用MB可降低血浆NO的水平，有助于创伤性休克的改善。     

The interaction between methylene blue and the cholinergic system

1. The inhibitory effects of methylene blue (MB) on different types of cholinesterases and [³H]-N-methylscopolamine ([³H]-NMS) binding to muscarinic receptors were studied.
2. Human plasma from young healthy male volunteers, purified human pseudocholinesterase and purified bovine true acetylcholinesterase were incubated with acetylcholine and increasing concentrations of MB (0.1–100 μmol l⁻¹) in the presence of the pH-indicator m-nitrophenol for 30 min at 25°C. The amount of acetic acid produced by the enzymatic hydrolysis of acetylcholine was determined photometrically.
3. Rat cardiac left ventricle homogenate was incubated with [³H]-NMS and with increasing concentrations of MB (0.1 nmol l⁻¹–100 μmol l⁻¹) at 37°C for 20 min. The binding of [³H]-NMS to the homogenate was quantified by a standard liquid scintillation technique.
4. MB inhibited the esterase activity of human plasma, human pseudocholinesterase and bovine acetylcholinesterase concentration-dependently with IC₅₀ values of 1.05±0.05 μmol l⁻¹, 5.32±0.36 μmol l⁻¹ and 0.42±0.09 μmol l⁻¹, respectively. MB induced complete inhibition of the esterase activity of human plasma and human pseudocholinesterase, whereas bovine acetylcholinesterase was maximally inhibited by 73±3.3%.
5. MB was able to inhibit specific [³H]-NMS binding to rat cardiac left ventricle homogenate completely with an IC₅₀ value of 0.77±0.03 μmol l⁻¹, which resulted in a K_i value for MB of 0.58±0.02 μmol l⁻¹.
6. In conclusion, MB may be considered as a cholinesterase inhibitor with additional, relevant affinity for muscarinic binding sites at concentrations at which MB is used for investigations into the endothelial system. In our opinion these interactions between MB and the cholinergic system invalidate the use of MB as a tool for the investigation of the L-arginine-NO-pathway, in particular when muscarinic receptor stimulation is involved.

     

亚甲蓝对感染性休克犬血液动力学和氧合功能的影响

目的　观察鸟苷酸环化酶抑制药亚甲蓝 (MB)对感染性休克犬血液动力学和氧合功能的影响。方法　采用内毒素静脉注入诱导的 1 1只感染性休克犬模型 ,输注 0 9%的氯化钠后 ,MB2mg/kg1 5分钟内静脉注入。经右颈内静脉放置的肺动脉导管测定基础、休克 1小时、输注生理盐水后和MB注入后 30、60、1 2 0、1 80分钟血液动力学 ,分析动脉、混合静脉血气和动脉血乳酸 ,计算氧合。结果　MB注入明显增加感染性休克犬平均动脉压 (MAP)、体血管阻力 (SVR)和左心室作功(LVSW) ,不影响肺动脉压 (PAP)、肺动脉嵌顿压 (PAOP)、心输出量 (CO)、氧输送 (DO2 )和氧摄取(VO2 ) (P >0 0 5)。MAP、SVR和LVSW的增高以 30分钟最为明显 ,分别从 (96 4± 1 6 6)mmHg、(4332 5± 75 8)dyne .sec .cm- 5、(1 4 0± 1 8) g .m升高到 (1 2 9 9± 1 8 3)mmHg、(52 67 1± 94 6)dyne.sec .cm- 5、(1 7 1± 2 6)g .m(P <0 0 1 ) ,1 80分钟基本回复。内毒素注入增加动脉血乳酸 (P <0 0 5) ;MB注入降低乳酸 ,1 2 0分钟最明显 ,从 (4 3± 1 3)mmol/L下降到 (3 4± 1 2 )mmol/L(P <0 0 5)。结论　MB注入改善感染性休克血液动力学 ,降低血乳酸 ,不影响氧合     

低浓度美蓝染色在乳头溢液手术中的应用

目的探讨乳管内低浓度美蓝染色并回抽的方法在乳头溢液患者手术中的作用。方法 43例乳头溢液行手术治疗的患者,随机分为改良组(低浓度美蓝染色并回抽)25例,传统手术组(乳管内高浓度美蓝染色)18例,分析两组术中美蓝外溢污染手术野以及微小病变的识别情况。结果 43例乳头溢液的病变导管均染色成功,改良组美蓝外溢污染手术野4例(16%),传统组8例(44.4%);改良法比传统方法更容易识别乳管微小病变。结论改良法对乳头溢液患者有应用价值。     

亚甲蓝对血浆HBsAg抗原性影响的实验观察

目的探讨利用亚甲蓝对HBsAg抗原性的影响作用。方法将不同浓度的HBsAg阳性血浆分别经亚甲蓝作用后,应用ELISA方法检测HBsAg变化情况,确定HBsAg是否被破坏。结果各浓度HBsAg经亚甲蓝作用后,其S/CO值均有不同程度的下降。结论亚甲蓝对HBsAg抗原性有一定破坏作用。     

亚甲基蓝对脑缺血再灌注大鼠血脑屏障的保护作用

目的 探讨亚甲基蓝对大鼠脑缺血再灌注损伤的保护作用及机制.方法 SD大鼠随机分为假手术组、模型组、亚甲基蓝低剂量组(1 mg/kg)、亚甲基蓝中剂量组(2 mg/kg)、亚甲基蓝高剂量组(4 mg/kg),每组12只.线栓法制备大鼠左侧颈动脉栓塞2 h再灌注24 h模型.亚甲基蓝组于术前1 d,再灌注时腹腔注射相应剂量...     

Ecotoxicological effects of alpha-cypermethrin on freshwater alga Chlorella sp.: Growth inhibition and oxidative stress studies

Alpha-cypermethrin (ACy) is a synthetic pyrethroid insecticide commonly used in agricultural practices for controlling a broad range of insect pests particularly belonging to the order Lepidoptera and Coleoptera. The present study aims to evaluate the toxic effect of ACy on microalgae by studying its influence on Chlorella sp. According to our knowledge, this is the first detailed study of ACy toxicity on microalgae. Significant growth inhibition of Chlorella sp. was observed at high ACy concentration (6−48 mg L⁻¹) during the entire 96 h bioassay. The 96 h median effective concentration (EC₅₀) of ACy was estimated to be 11.00 mg L⁻¹. Flow cytometry analysis showed an enhanced generation of reactive oxygen species (ROS) and intracellular lipid accumulation after 96 h exposure to 11.00 mg L^-1 of ACy. Further, the same ACy concentration showed a significant decrease in photosynthetic pigment content and an increase in antioxidant enzyme activity and malondialdehyde (MDA) content in Chlorella sp.     

Iron metabolism and toxicity

Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer.