依达拉奉在脊髓型颈椎病围手术期应用的效果观察

目的:探讨自由基清除剂依达拉奉在脊髓型颈椎病围手术期应用的价值。方法:前路减压、植骨内固定治疗58例脊髓型颈椎病,治疗组30例患者围手术期应用依达拉奉,术前30min静脉滴注(30mg),术后连续使用6d(30mg/次,2次/d);对照组28例,未应用依达拉奉。采用电子自旋共振(electronspinresonance,ESR)检测患者术前30min、减压后30min脑脊液自由基含量;术前及术后1d、1周、3个月采用JOA评分评定神经功能,观察术后症状反跳发生率。结果:脑脊液自由基含量术前两组无明显差异(P>0.05),减压后30min治疗组较对照组明显减少(P<0.05)。术前、术后1d、术后3个月治疗组与对照组JOA评分无明显差异(P>0.05),术后1周治疗组JOA评分优于对照组(P<0.05)。治疗组术后症状反跳的发生率、持续时间均低于对照组(P<0.05)。结论:脊髓型颈椎病患者围手术期应用自由基清除剂依达拉奉,能降低脑脊液自由基浓度,减少术后症状反跳,提高术后短期疗效。     

自由基在地方性甲状腺肿发病学上的可能作用

对缺碘地区的正常人，甲状腺生理肿大及Ⅱ度甲状腺肿三组人群进行了细胞抗氧化能力和免疫功能的测定。结果表明，缺碘可以导致ＬＰＯ含量增高；ＳＯＤ活性下降；ＩｇＡ和ＩｇＭ含量增高，ＴＲＡｂ阳性检出率升高。因缺碘而致的细胞抗氧化能力下降及自由基的损伤作用可能诱发甲状腺自家免疫的发生，自由基损伤作用导致的自家免疫的病理过程可能是地甲肿发病学中的一个重要继发环节。     

一氧化氮中介雷米普利拉对氧自由基损伤兔胸主动脉内皮的保护作用

采用离体兔胸主动脉淋浴灌注方法，探讨雷米普利拉（Ｒａｍ）对氧自由基损伤血管内皮功能的保护作用及其机理．结果发现，电解Ｋｒｅｂｓ液产生的氧自由基明显抑制血管内皮依赖性舒张，降低血管壁氧化氮（ＮＯ）和ｃＧＭＰ含量，并使丙二醛含量增加；Ｒａｍ消除电解所致的上述作用，并呈现剂量依赖性；ＮＯ合成的前体物质─—Ｌ－精氨酸亦具有相似的保护作用；Ｒａｍ和Ｌ－精氨酸的保护作用均可被ＮＯ合成酶抑制剂所阻断。这些结果提示，Ｒａｍ抗氧自由基损伤血管内皮的作用可能与其促进内皮细胞合成，释放ＮＯ有关。Ｐ＜０．０１，ｃｏｍｐａｒｅｄｗｉｔｈｃｏｎｔｒｏｌ．Ｐ＜０．０５，Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＥｌｅ；Ｐ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＲａｍΔΔＰ＜０．０１．ｃｏｍｐａｒｅｄｗｉｔｈＬ－Ａｒｇ．ＳｉｍｉｌａｒｒｅｓｕｌｔｗａｓｏｂｔａｉｎｅｄｉｎｔｈｅｔｉｓｓｕｅｔｒｅａｔｅｄｗｉｔｈＬ－Ａｒｇ．Ｈｏｗｅｖｅｒ．ｔｈｅｅｆｆｅｃｔｏｆＲａｎｉｏｒＬＡｒｇｗａｓａｂｒｏｇａｔｃｄｉｎｔｈｅｐｒｅｓｅｎｃｅｏｆＮＡｒｇ．Ｒｅｄｕｃｔｉｏｎｂｙｅｌｅｃｔｒｏｌｙｓｉｓｏｆｎｉｔｒｉｔｅｖａｌｕｅｗａｓｎｏｔｉｎｆｌｕｅｎｃｅｄ?     

Hypoxia-induced free iron release in the red cells of newborn infants*

Heparinized blood samples were obtained at birth from 164 newborn infants (101 full term; 63 preterm). Intra-erythrocyte free iron concentration and hypoxanthine plasma levels were determined by high-pressure liquid chromatography. Intra-erythrocyte free iron concentration was higher in preterm than in full term babies (p < 0:0001) and adults (p < 0:0001). Statistically significant correlations were observed between intra-erythrocyte free iron concentration and hypoxanthine levels (r = 0:66; p= 0:0001), pH (r = - 0:76; p = 0:0001), base excess (r = - 0:79; p= 0:0001), and gestational age (r = - 0:44; p= 0:0001) in both infant populations. Multiple regression analysis between intra-erythrocyte free iron concentration in cord blood, as an independent variable, and Apgar score at 1 min, pH, base excess, hypoxanthine values, FiO₂ needed for resuscitation immediately after delivery, and gestational age, as dependent variables, identified hypoxanthine levels (p= 0:0003; partial F-test = 15.4) as the best single predictor of intra-erythrocyte free iron concentration. In conclusion, hypoxia induces intra-erythrocyte free iron release, and therefore enhances the risk of oxidative injury due to hydroxyl radical generation.     

Molecular mechanisms in “stunned” myocardium

Summary In a recent overview on stunning, Bolli [1] listed the three pillars on which theories on stunning rest: its causation by oxygen radicals, the amplification of damage by Ca²⁺ overload, and the resulting excitation contraction uncoupling. Our own experiments with SOD and catalase do not convince us that stunning is caused by free radicals, because we and others were unable to show improvement. An important pathway of radical generation, i.e., xanthine oxidase, does not exist in the hearts of several families of mammals, but stunning can of course be produced in these species. We agree with Bolli that stunning represents a disturbance of electromechanical coupling, but we acknowledge the controversy that exists with regard to the subcellular seat of the defect. Our results would support hypotheses that pinpoint the defect to the sarcoplasmic reticulum. However, the possibility of multiple defects should also be considered: Our finding of altered Ca²⁺ ATPase expression and Kusuoka's finding of altered myofibrillar Ca²⁺ sensitivity are not necessarily mutually exclusive but may be complementary, or may represent different stages of ischemic damage. Our finding of decreased myosin expression may help to explain the long persistence of the contractile defect. From the available evidence, the hypothetial possibility evolves that stunning is not just an injury, but rather the unmasking of a regulatory mechanism to protect the heart against premature or further damage. The observation that coronary occlusion causes both stunning and preconditioning by a parallel, and not by a sequential, mechanism and that a multitude of genes alter their expression in order to protect the myocyte argue for a regulatory change.     

The incidence of testosterone deficiency in men with long-term spinal cord injury

BackgroundThe testosterone deficiency syndrome (TDS) is increasingly recognized as a distinct entity, especially in aging men, and is characterized by typical clinical and biochemical effects. These include sexual dysfunction, mood alterations, loss of lean muscle, skin changes, osteoporosis, and changes in visceral fat. The same clinical features occur in men with a spinal cord injury (SCI). This study was carried out to determine the incidence of testosterone deficiency in men with a long standing SCI and to examine the possible need for testosterone replacement therapy for such men.MethodsForty-two long-term SCI men with an average age of 54 years and average time of 20 years since injury were studied. Their serum total testosterone (TT) and serum sex hormone binding globulin (SHBG) levels were measured and free testosterone levels were calculated.ResultsThe serum TT levels were all well above the recommended normal lower limit of 12 nmol/l. The average serum TT level was 17.4 nmol/l. The serum SHBG levels were above the lower limit of normal of 13 nmol/l and below the upper limit of normal of 70 nmol/l. The average SHBG level was 37.5 nmol/l, which is well within normal limits. The calculated free testosterone levels were all well above the recommended lower limit of normal of 225 pmol/l. The average free testosterone level was well above this level at 348 pmol/l. All these levels were within the current internationally recommended normal range.ConclusionsIn this group of 42 men with long-term SCI the serum TT, SHBG, and free testosterone levels were normal. However, there are still large gaps in available information and further studies are recommended.     

Free radical scavenging alleviates the biomechanical impairment of gamma radiation sterilized bone tissue.

Terminal sterilization of bone allografts by gamma radiation is often essential prior to their clinical use to minimize the risk of infection and disease transmission. While gamma radiation has efficacy superior to other sterilization methods it also impairs the material properties of bone allografts, which may result in premature clinical failure of the allograft. The mechanisms by which gamma radiation sterilization damages bone tissue are not well known although there is evidence that the damage is induced via free radical attack on the collagen. In the light of the existing literature, it was hypothesized that gamma radiation induced biochemical damage to bone's collagen that can be reduced by scavenging for the free radicals generated during the ionizing radiation. It was also hypothesized that this lessening of the extent of biochemical degradation of collagen will be accompanied by alleviation in the extent of biomechanical impairment secondary to gamma radiation sterilization. Standardized tensile test specimens machined from human femoral cortical bone and specimens were assigned to four treatment groups: control, scavenger treated-control, irradiated and scavenger treated-irradiated. Thiourea was selected as the free radical scavenger and it was applied in aqueous form at the concentration of 1.5 M. Monotonic and cyclic mechanical tests were conducted to evaluate the mechanical performance of the treatment groups and the biochemical integrity of collagen molecules were assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native mechanical properties of bone tissue did not change by thiourea treatment only. The effect of thiourea treatment on mechanical properties of irradiated specimens were such that the post-yield energy, the fracture energy and the fatigue life of thiourea treated-irradiated treatment group were 1.9-fold, 3.3-fold and 4.7-fold greater than those of the irradiated treatment group, respectively. However, the mechanical function of thiourea treated and irradiated specimens was not to the level of unirradiated controls. The damage occurred through the cleavage of the collagen backbone as revealed by SDS PAGE analysis. Irradiated specimens did not exhibit a noteworthy amount of intact alpha-chains whereas those irradiated in the presence of thiourea demonstrated intact alpha-chains. Results demonstrated that free radical damage is an important pathway of damage, caused by cleaving the collagen backbone. Blocking the activity of free radicals using the scavenger thiourea reduces the extent of damage to collagen, helping to maintain the mechanical strength of sterilized tissue. Therefore, free radical scavenger thiourea has the potential to improve the functional life-time of the allograft component following transplantation.     

Pharmacology of Neural Tube Defects

Summary:  The pharmacology of neural tube defects (NTDs) is a complex issue. Several theories regarding the etiology of NTDs emphasize the importance of interactions between genetic, environmental, and biochemical factors at a key point in time. One such factor is chronic drug therapy, a potential consequence of which is the formation of toxic drug metabolites, including free radicals (FRs), which have been implicated in the etiology of NTDs. Under normal physiological conditions, FRs are quickly destroyed by antioxidant defense systems. However, FR-mediated cellular damage can occur if these defense systems fail or are overburdened, such as in patients who are genetically deficient in FR scavenging enzyme activity (FRSEA) or who are receiving chronic drug therapy. Congenital defects, including NTDs, resulting from FR-induced damage have been reported in both experimental animals and humans. For example, the use of antiepileptic drugs (AEDs) during pregnancy that have the propensity to form FRs during their metabolism are associated with an increased risk of the development of congenital malformations, including NTDs. This article reviews the biochemistry of FRs, the factors regulating FR scavenging capacity, and the theories regarding the etiology of NTDs; presents a hypothesis of a unified mechanism for AED-induced NTDs and other congenital defects; and briefly discusses the roles of folate and selenium in the prevention of NTDs.