3—氯—4—氟苯胺的生产与研究概况

评述了3-氯-4-氟苯胺的实验室研究和工业生产现状,特别对氯化、硝化、氟化和还原等反应中间体的制备及其质量作了分析。     

肉鸡对不同形态锰源的生物利用率研究

目的 :　研究肉仔鸡对不同形态锰源的相对生物学利用率。方法 :　将 62 4只 1日龄肉公鸡随机分为 1 3组 ,分别饲不添加锰的基础饲粮 (对照组 )或以不同锰化合物添加 60、1 2 0、1 80 mg/ kg锰的试验饲粮 2 1 d。结果 :　肉鸡生长性能各指标和腿病发生率以及肉鸡的跖骨灰锰含量、心肌细胞线粒体中 Mn SOD活性均未受到添加锰源以及锰源与锰水平互作的显著影响 ,但受到添加锰水平的显著影响。肉鸡心肌含锰量和 Mn SOD m RNA水平均未受到添加锰源与锰水平互作的显著影响 ,但受到添加锰源及添加锰水平的显著影响。其中中等和强络合强度有机锰源的生物学利用率明显高于无机硫酸锰和弱络合强度有机锰源。结论 :　中等和强络合强度的复合氨基酸锰对肉仔鸡的生物学利用率明显优于无机硫酸锰和弱络合强度的蛋氨酸锰     

Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine

Calorie restriction (CR) extends the life span of various species through mechanisms that are as yet unclear. Recently, we have reported that mitochondrion-mediated apoptosis was enhanced in alphaMUPA transgenic mice that spontaneously eat less and live longer compared with their wild-type (WT) control mice. To understand the molecular mechanisms underlying the increased apoptosis, we compared alphaMUPA and WT mice for parameters associated with SOD2 (MnSOD), a mitochondrial antioxidant enzyme that converts superoxide radicals into H(2)O(2) and is also known to inhibit apoptosis. The SOD2-related parameters included the levels of SOD2 mRNA, immunoreactivity and enzymatic activity in the liver, lipid oxidation and aconitase activity in isolated liver mitochondria, and the sensitivity of the mice to paraquat, an agent that elicits oxidative stress. In addition, we compared the mice for the levels of SOD2 mRNA after treatment with bacterial lipopolysaccharides (LPS), and for the DNA binding activity of NFkappaB as a marker for the inflammatory state. We extended SOD2 determination to the colon, where we also examined the formation of pre-neoplastic aberrant crypt foci (ACF) following treatment with dimethylhydrazine (DMH), a colonic organotypic carcinogen. Overall, alphaMUPA mice showed reduced basal levels of SOD2 gene expression and activity concomitantly with reduced lipid oxidation, increased aconitase activity and enhanced paraquat sensitivity, while maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. alphaMUPA mice also showed increased resistance to DMH-induced pre-neoplasia. Collectively, these data are consistent with a model, in which an optimal fine-tuning of SOD2 throughout a long-term regimen of reduced eating could contribute to longevity, at least in the alphaMUPA mice.     

L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency

L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.     

锰超氧化物歧化酶过表达对H2O2诱导PC12细胞凋亡的影响

目的 揭示锰超氧化物歧化酶（MnSOD）在H2O2诱导PC12细胞凋亡中的作用及机制。方法 转染人正义和反义MnSOD基因的PC12细胞,用50 mmol H2O2攻击已转染的细胞系,并采用MTT法、流式细胞术和 Hoechst染色方法研究H2O2的细胞毒作用。结果 转染正义MnSOD的细胞比原细胞的MnSOD酶活性提高1.3倍,而转染反义MnSOD细胞的酶活性降低67%。结论 H2O2对PC12细胞毒作用是通过诱发PC12细胞凋亡作用来实现的;MnSOD具有抑制H2O2诱导PC12细胞凋亡作用,涉及线粒体的损伤,导致氧化还原失衡继而诱发细胞凋亡。     

A mitochondrial superoxide theory for oxidative stress diseases and aging

Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O₂^•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q₁₀) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.     

Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10–4.59 and P = 0.032 OR 2.32 CI 1.07–5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.     

苔藓蒽噻吩-1-羧酸甲酯的合成

目的 高效合成目标分子苔藓蒽噻吩-1-羧酸甲酯.方法 以1,8-二羟基-9,10-蒽醌为原料,经过保护、硝化、巯代、环合和脱保护5步反应,合成目标分子.结果 以45.8%的总收率合成目标分子.结论 高效合成了苔藓蒽噻吩-1-羧酸甲酯.本方法具有合成路线短、选择性好和合成效率高等特点.