Pathogenesis of progressive muscular dystrophy: studies on free radical metabolism in an animal model

Evidence to suggest the presence of abnormal metabolism of oxygen free radicals in progressive muscular dystrophy is presented using an animal model. In the superficial pectoral muscles of dystrophic chickens, enzyme activities regulating the metabolism of oxygen free radicals, i.e., catalase, superoxide dismutases and glutathione peroxidase, were significantly elevated within 1 week of hatching. Activities of related enzymes, i.e., glutathione reductase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase were also elevated. In contrast, the specific activity of phosphofructokinase, the rate-limiting enzyme of the glycolytic pathway, was normal during the first 4-week period. These results suggest that there is an increased turnover of oxygen free radicals in the dystrophic muscle. This concept appears important in a further investigation of the pathogenesis and treatment of progressive muscular dystrophies.     

缺血－再灌注兔心肌肌浆网自由基的测定

应用电子自旋共振波谱仪（ＥＳＲ）直接检测了缺血－再灌注兔心肌肌浆网自由基的变化，以探讨肌质网系统与氧自由基的关系。实验中将２０只兔随机分为再灌注对照组、超氧化物歧化酶（ＳＯＤ）组、ＡＴＰ－氯化镁组和人参皂甙Ｒｅ组。实验结果，ｇ值２．００４６处为半醌自由基波谱，其相对浓度各组依次为７８．９４±２．１２６，１４．４６±２．８６，２０．６５±７．６５，１４．６６±３．６７（ｘ±ＳＤ），对照组与用药组均有显著性差异（Ｐ＜０．０５），表明缺血－再灌注兔心肌肌浆网产生大量的自由基，用ＥＳＲ可以直接检测到半醌自由基，外源性高能磷酸盐制剂ＡＴＰ－氯化镁及人参皂甙Ｒｅ与超氧化物歧化酶一样，发挥清除兔心肌肌浆网自由基的作用。     

Transcranial cerebral oximetry and carotid cavernous fistula occlusion

Summary Different methods have been used in the evaluation and monitoring of the cerebral oxygen supply during neuro-interventional therapies. Attenuation of near-infrared light by the chromophores oxyhemoglobin and deoxyhemoglobin have shown to be useful in the study of the cellular oxygen metabolism and oxygen delivery to the brain. Transcranial cerebral oximetry (TCCO) has the advantage of providing real-time information regarding regional brain oxygen saturation (rSO₂) by using wavelengths in the near-infrared range.We present a patient with a carotid cavernous fistula who underwent balloon occulusion and concurrent continuous TCCO monitoring. TCCO was found to be a useful tool providing immediate rSO₂ values during the angiographic and interventional procedures. Initial balloon occlusion of a carotid cavernous fistula resulted in partial occlusion of the internal carotid artery lumen causing an immediate decrease in rSO₂ which correlated with angiographic findings. Subsequent reocclusion of the fistula produced a slower and smaller degree of decrease in rSO₂ with clinical improvement in the patient. Changes in rSO₂ were detected before any adverse clinical event was observed. TCCO was reliable, safe, sensitive, and provided a real-time assessment tool for the monitoring of brain oxygen supply in a patient undergoing a neuroendovascular procedure.     

Environmental effects on the growth and proteolysis of Treponema denticola ATCC 33520

The effect of pH, redox potential, O₂ and H₂ on the growth and proteolytic activity of Treponema denticola ATCC 33520 was studied in a chemostat at different growth rates. The peptidase and protease activities were estimated using different amido-methyl coumarin derivatives and azocasein. The maximum growth rate of T. denticola ATCC 33520 was 0.14 h⁻¹. Reduction of the growth rate of T. denticola by 50–60% gave: an increase in cell mass of 150–200%, a higher acetogenesis and a shift of the pH optimum. The protease and phenylalanine peptidase activities seemed to be of greater importance for the growth of T. denticola ATCC 33520 than the rather low arginine and proline peptidase activities. The redox potential (E_h) played a secondary role. At microaerophilic conditions with 1–5% O₂, the cultures maintained a redox potential below −311 mV and an optimal acetogenesis. The presence of H? induced a marked growth stimulation of T. denticola ATCC 33520. It is concluded that the cell mass and proteolytic activity of T. denticola ATCC 33520 are modulated by the growth rate and the pH and to a lesser extend by the redox potential and presence of O₂. Stagnation of the exudate-flow influences these factors and will lead to an increase of the spirochetal population and proteolysis in the periodontal pocket.     

抗氧化剂等药物联合应用治疗烧伤休克的实验研究

我们用哈白兔以3％凝固气油致25％Ⅲ°烧伤休克持续了3h复苏的动物模型研究了丹参、维生素E、抗氧化剂协同治疗烧伤休克的作用,效果显著。第5天SOD活性和MDA值均达到伤前水平,提高了动物存活时间。各项生化指标和病理证实,该组实验动物脏器无明显病变,说明联合用药,不仅可以有效的清除氧自由基,还能拮抗脂质过氧化作用,对脏器有较好的保护作用。     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Andrology: Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparations and seminal plasma

The addition of luminol to unprocessed semen samples resultedin the generation of chemiluminescent signals, the intensityof which was highly correlated with the level of leukocyte contamination.Despite the spontaneous oxidant-generating capacity of seminalleukocytes, no correlations were observed between leukocytecontamination and the fertility status of the subjects or anyaspect of the semen profile, including the motility of the spermatozoaor their performance in a hyaluronate penetration assay. Luminol-dependentchemiluminescence and leukocyte contamination were also correlatedin washed sperm suspensions prepared either by repeated centrifugationor on discontinuous Percoll gradients. However, in such spermsuspensions, the spontaneous generation of oxidants by contaminatingleukocytes (>2x10⁴ leukocytes/ml) was invariably associatedwith a decreased capacity for movement. Moreover, causativeassociations between leukocyte contamination, reactive oxygenspecies generation, lipid peroxidation and impaired sperm motilitywere revealed by experiments involving the selective additionor removal of activated leukocytes. From these observationswe can conclude that low concentrations of leukocytes are acommon feature of the human ejaculate and can impair sperm function,particularly in the absence of seminal plasma. These findingshave implications for our understanding of the importance ofleukocytospermia in defining the fertility of human spermatozoain vivo and in vitro.     

Preventing percutaneous absorption of industrial chemicals: the "skin" denotation

Percutaneous absorption has received comparatively little attention in occupational health, although this route of entry has repeatedly caused occupation-related intoxications. In practice, the evaluation of skin penetration rates is far from simple. Much evidence has been obtained from studies of chemicals used for cosmetics and topical therapeutics, but the information available on compounds encountered in occupational health is limited. The data obtained from experimental studies have confirmed that the concentration, type of vehicle, skin area, skin condition, and extent of occlusion are important factors in determining the degree of percutaneous absorption, but no general model has been developed. Also, too little is known about the basic chemical properties governing the rate of penetration. Thus, prediction is difficult and bound to be rather inaccurate. Current preventive practice follows the procedure used by ACGIH and is mainly based on a "skin" denotation in official listings of chemicals to which exposure limits have been allocated. The number of substances and groups of chemicals which have received skin denotation in 17 selected countries varies between 24 and 179 and a total of 275 are listed as a skin hazard in one or more countries; ACGIH lists 143. Thus, the denotation practice varies. As an unfortunate result of these discrepancies and the dichotomy of skin denotation, the absence of skin denotation may erroneously indicate that efforts to protect the skin are unnecessary. Thus, an evaluation of skin penetration potentials should be incorporated in occupational health practice as a supplement to the official denotations.