Benznidazole, a drug employed in the treatment of Chagas' disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages.

Benznidazole (BZL) is a nitroheterocyclic drug employed in the chemotherapy of Chagas' disease, a protozoan disease caused by Trypanosoma cruzi. Because this parasite mostly replicates in macrophages, we investigated whether BZL was likely to modify the synthesis of macrophage mediators such as nitrite, tumour necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6 and IL-10. Control and stimulated murine macrophages (lipopolysaccharide (LPS) and/or interferon-gamma (IFN-gamma)) were treated with BZL and measurements were carried out in culture supernatants collected 24 h later. Synthesis of nitrite, IL-6 and IL-10 was maximal upon combined stimulation with LPS + IFN-gamma, whereas lower amounts of the three mediators were detected when both stimuli were given alone. BZL treatment significantly reduced nitrite, IL-6 and IL-10 production, to undetectable levels in some cases, particularly IL-6 and IL-10. LPS was the most potent stimulus of IL-1beta and TNF-alpha production, followed by LPS + IFN-gamma and IFN-gamma in decreasing order. BZL partly inhibited TNF-alpha synthesis, but this effect was smaller than that observed for nitrite, IL-6 and IL-10. LPS-induced production of IL-1beta was also affected by BZL. Semiquantification of gene expression for inducible nitric oxide synthase (iNOS) showed that BZL completely inhibited iNOS gene induction by IFN-gamma, and resulted in respective inhibitions of 30% and 50% with LPS- and LPS + IFN-gamma-stimulated cells. BZL was not cytotoxic on macrophage cultures, as shown by the lactate dehydrogenase activity. Besides its trypanocidal activity, BZL may also alter the balance between pro- and anti-inflammatory mediators with important consequences for the course of T. cruzi infection.     

Effect of inhaled nitric oxide on endotoxin-induced hypoxaemia in rabbits

In five mechanically ventilated rabbits, we studied the property of inhaled nitric oxide in helping to treat hypoxaemia which was induced by intravenous endotoxin (Escherichiacoli-derived lipopolysaccharide, serotype 0111: B4). We used measurements of arterial partial pressure of oxygen to check a therapeutic nitric oxide benefit. Pulmonary artery pressure was continuously monitored. Furthermore, we determined the single-breath diffusing capacity for nitric oxide. Measurements of plasma nitrite/nitrate concentration served as an indicator of endogenous nitric oxide output. The first infusion of endotoxin led to a transient pulmonary vasoconstriction, whereas arterial partial pressure of oxygen was permanently reduced by 30 ± 10 mmHg (mean ± SD), attaining minimal values of 48 ± 3.4 mmHg due to additional endotoxin. Single-breath diffusing capacity for nitric oxide declined by 20 ± 5.5% of baseline values until the experiments were concluded. Endotoxin induced an increase in plasma nitrite/nitrate concentration in the five rabbits as well as in the control animals (four rabbits) without exogenous nitric oxide supply. During the 25 inhalations of nitric oxide (3–50 ppm), arterial oxygenation did not change significantly. Thus endotoxin permanently impaired pulmonary gas exchange without inducing pulmonary hypertension. Inhaled nitric oxide did not improve arterial oxygenation during endotoxaemia.     

Type 2 nitric oxide synthase and protein nitration in chronic lung infection

Inflammation in the lung can lead to increased expression of inducible nitric oxide synthase (iNOS) and enhanced NO production. It has been postulated that the resultant highly reactive NO metabolites may have an important role in host defence, although they might also contribute to tissue damage. However, in a number of inflammatory lung diseases, including bronchiectasis, iNOS expression is increased but no elevation of airway NO can be detected. A potential explanation for this finding is that NO is rapidly scavenged by reaction with superoxide radicals, forming peroxynitrite, which is preferentially metabolized via nitration and nitrosation reactions. To test this hypothesis, anaesthetized, specific pathogen-free rats were inoculated with Pseudomonas aeruginosa incorporated into agar beads (chronically infected group) or sterile agar beads (control group). Ten to 15 days later, the lungs were isolated and fixed. Pseudomonas organisms were isolated from the lungs of the chronically infected group. These lungs showed extensive inflammatory cell infiltration and tissue damage, which were not observed in control lungs. Expression of iNOS was increased in the chronically infected group when compared with the control group. However, the mean number of cells staining for nitrotyrosine in the chronically infected group was not significantly different from that in the controls, nor was there an excess of nitrotyrosine, nitrate, nitrite or nitrosothiol concentrations in the infected lungs. Thus, no evidence was found of increased NO metabolites in chronically infected lungs, including products of the peroxynitrite pathway. These findings suggest that chronic infection does not cause increased iNOS activity in the lung, despite increased expression of iNOS.     

覆盆子不同提取部位对小鼠记忆障碍的改善作用研究

目的:观察覆盆子不同提取部位对东莨菪碱、亚硝酸钠及40%乙醇造成的小鼠记忆障碍模型的影响,探索覆盆子对这3种记忆障碍模型的有效部位,为进一步研究覆盆子对学习记忆改善作用的机制提供依据。方法:昆明种小鼠130只,随机分成13组,每组10只。即正常组,模型组,阳性组,覆盆子全药高剂量和低剂量组,三氯甲烷部位高剂量和低剂量组,正丁醇部位高剂量和低剂量组,乙酸乙酯部位高剂量和低剂量组,水提部位高剂量和低剂量组。给药组小鼠分别以高、低剂量(24,12 g·kg~(-1))ig覆盆子全药、三氯甲烷部位、正丁醇部位、乙酸乙酯部位、水提部位;阳性药组给银杏叶制剂量为7.6 mg·kg~(-1),正常组和模型组给予等量的蒸馏水,连续12 d。7 d后除正常组外,东莨菪碱所致模型测试前30 min ip 1 mg·kg~(-1),亚硝酸钠所致模型训练后ip 120 mg·kg~(-1),40%乙醇所致模型测试前30 min ig 0.1 m L·kg~(-1),检测小鼠在Morris水迷宫的定位航行能力和空间探索能力。结果:与正常组比较,3种记忆障碍逃避潜伏期明显延长,穿越平台次数明显缩短(P0.05);与模型组比较,覆盆子全药、三氯甲烷部位、正丁醇部位、乙酸乙酯部位、水提部位均可缩短3种记忆障碍逃避潜伏期,增加其穿越平台次数(P0.05)。结论:覆盆子水提部位高剂量组对东莨菪碱、亚硝酸钠造成的小鼠记忆障碍模型改善效果最优;覆盆子全药高剂量组对40%乙醇造成的记忆障碍小鼠模型改善效果最优。     

一起亚硝酸盐污染自来水管网的急性中毒暴发事件调查

目的寻找及分析因井水亚硝酸盐污染自来水管网导致中毒暴发事件的原因。方法根据流行病学调查、环境卫生现场调查资料和水质检验结果分析事故。结果事故工厂生产工艺需用大量亚硝酸钠和水,生产区有一工业用井水,生产区内井水亚硝酸钠严重超标,井水管道与镇自来水管网相通,事故原因是井水亚硝酸钠污染自来水引起的19例人员亚硝酸盐中毒。结论工厂违反饮用水卫生规范要求,擅自将井水管道与镇自来水管网相连接,有关部门缺乏对工厂饮用水安全的检查。     

格列齐特中亚硝酸盐的电化学测定法

目的：建立高效液相-电化学(ECD)检测法测定格列齐特中亚硝酸盐(NO2^-)的残留量。方法：阳离子色谱柱，醋酸盐缓冲液(pH为4．3)为流动相。结果：NO2^-线性范围0．04～0．80μg，r=0．9995，回收率为99．2％，RSD=1．7％(n=9)。结论：方法灵敏，简便，结果准确，     

大蒜与胃癌Ⅱ——大蒜对胃液硝酸盐还原菌生长及产生亚硝酸盐的抑制作用

本文报导常吃大蒜的胃癌低发区苍山县居民胃液中活菌总数、硝酸盐还原菌检出率和胃液pH值均显著低于少吃大蒜的胃癌高发区栖霞县。体外实验进一步证实大蒜匀浆、乙基硫代磺酸乙酯和二烯丙三硫对从受检人胃液中分离出的硝酸盐还原菌的生长及产生亚硝酸盐均有明显的抑制作用。由此可提示前文报导常吃大蒜居民胃液中亚硝酸盐含量显著低于少食大蒜者,其原因可能是由于大蒜对胃液中细菌,特别是对硝酸盐还原菌的抑杀作用。     

A short history of nitroglycerine and nitric oxide in pharmacology and physiology

1. Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent headache' produced by minute quantities of NG on the tongue. 2. Constantin Hering, in 1849, tested NG in healthy volunteers, observing that headache was caused with 'such precision'. Hering pursued NG ('glonoine') as a homeopathic remedy for headache, believing that its use fell within the doctrine of 'like cures like'. 3. Alfred Nobel joined Pelouze in 1851 and recognized the potential of NG. He began manufacturing NG in Sweden, overcoming handling problems with his patent detonator. Nobel suffered acutely from angina and was later to refuse NG as a treatment. 4. During the mid-19th century, scientists in Britain took an interest in the newly discovered amyl nitrite, recognized as a powerful vasodilator. Lauder Brunton, the father of modern pharmacology, used the compound to relieve angina in 1867, noting the pharmacological resistance to repeated doses. 5. William Murrell first used NG for angina in 1876, although NG entered the British Pharmacopoeia as a remedy for hypertension. William Martindale, the pharmaceutical chemist, prepared '...a more stable and portable preparation': 1/100th of a grain in chocolate. 6. In the early 20th century, scientists worked on in vitro actions of nitrate-containing compounds although little progress was made towards understanding the cellular mode of action. 7. The NG industry flourished from 1900, exposing workers to high levels of organic nitrites; the phenomena of nitrate tolerance was recognized by the onset of 'Monday disease' and of nitrate-withdrawal/overcompensation by 'Sunday Heart Attacks'. 8. Ferid Murad discovered the release of nitric oxide (NO) from NG and its action on vascular smooth muscle (in 1977). Robert Furchgott and John Zawadski recognized the importance of the endothelium in acetylcholine-induced vasorelaxation (in 1980) and Louis Ignarro and Salvador Moncada identified endothelial-derived relaxing factor (EDRF) as NO (in 1987). 9. Glycerol trinitrate remains the treatment of choice for relieving angina; other organic esters and inorganic nitrates are also used, but the rapid action of NG and its established efficacy make it the mainstay of angina pectoris relief.     

瓜蒌皮抗缺氧作用的研究

实验结果显示，瓜蒌皮提取液（ＥＰＴ）腹腔注射４０ ｇ·ｋｇ－１能明显延长常压缺氧、组织缺氧、特异性心肌缺氧小鼠的存活时间，延长率分别为 １４５％， ２．７９％， １１０．７％，使减压缺氧小鼠的存活率达８５％．表明瓜蒌皮确能增强整体动物的抗缺氧能力．     

Effects of 4-dimethylaminophenol,Co2EDTA,or NaNO2 on cerebral blood flow and sinus blood homeostasis of dogs in connection with acute cyanide poisoning

The effects of the cyanide antidotes DMAP, Co₂EDTA, and NaNO₂ on cerebral blood flow (CBF) and cerebral blood gases were investigated in connection with acute poisoning of dogs by cyanide. The substances were injected intravenously. Local CBF as measured with thermocouples in the cingulum increased by 100–200% after a non-lethal dose of KCN (1 mg/kg) and by 50% after injection of NaNO₂ (15 mg/kg), that oxidized some 20% of the total hemoglobin to ferrihemoglobin. Co₂EDTA (10 mg/kg) induced a decrease in local CBF of 30% and in brain temperature of 0.5°C. The temperature diminished also after poisoning by KCN, but it rose by 0.15°C after the administration of NaNO₂. Local CBF and sinus sagittalis blood flow increased by 60–160% for about 15 min, and the brain temperature decreased by 0.4–0.5°C when DMAP (3.25 mg/kg) or Co₂EDTA (15 mg/kg) was injected 1 min after poisoning by cyanide (4 mg/kg), a dose that always caused respiratory arrest. Immediately after injection of DMAP the brain temperature rose transiently by 0.1–0.2°C. Co₂EDTA did not exert such an effect. In the sinus sagittalis blood of artificially ventilated animals pCO₂ decreased rapidly by 10–20 mmHg after poisoning and approached the initial level after treatment with DMAP or Co₂EDTA. The highest value of pO₂ was about 80 mmHg and 50 mmHg after injection of DMAP and Co₂EDTA, respectively; thereafter pO₂ declined to 20 mmHg or 40 mmHg at 20 min. The lactate concentration increased by 60–70% without tendency to return to normal.