Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

火药爆炸复合烧伤大鼠血浆CK-MB与心肌MDA变化

目的 探讨烟花火药爆炸复合烧伤大鼠血浆肌酸激酶心肌同工酶(CK—MB)与心肌丙二醛(MDA)含量的变化。方法 Wistar大鼠128只，随机分为正常对照组(n=8)、烧伤组(n=40)、爆炸伤组(n=40)和复合伤组(n=40)，分别致伤形成大鼠20％体表面积Ⅲ度烧伤、火药爆炸伤和两者复合伤。动态观察大鼠伤后1、3、6、12、24h血浆CK—MB，心肌MDA含量并进行相关分析。结果 复合伤组较单因素致伤组大鼠血浆CK—MB升高明显，心肌组织MDA含量呈类似变化，CK—MB与MDA有相关性。结论 烟花火药爆炸复合烧伤对大鼠心肌的损害较单纯烧伤或爆炸伤更为严重，提示烧伤和爆炸伤有协同致伤作用，氧自由基代谢紊乱参与烟花火药爆炸复合烧伤后心肌的损伤。     

A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene

Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene.     

Metabolite changes with age measured by proton magnetic resonance spectroscopy in normal subjects

Abstract  To determine whether there are metabolite changes in the left medial temporal and frontal lobes with aging, we performed proton magnetic resonance spectroscopy in 36 normal subjects. The N-acetylaspartate/creatine-phosphocreatine ratio in the medial temporal lobe tended to be decreased in subjects over 60 years of age. The ratio decrease in the frontal lobe related to aging was lower than that in the medial temporal lobe. There were no significant differences in the metabolite ratios between males and females. These findings suggest that structures in the medial temporal lobe may be more susceptible to neuronal dysfunction associated with aging than those in the frontal lobe.     

肉苁蓉总苷对阿霉素所致小鼠心肌毒性的保护作用

目的：探讨肉苁蓉总苷（GCs)对阿霉素（Dox)所致小鼠心肌损害的保护作用及其机制。方法：选用NIH小鼠一次腹腔注射Dox(17.5mg/kg)造成急性心肌损伤模型，测定心肌超氧化物歧化酶（SOD）活性；硒－谷胱苷肽过氧化物酶（Se-GSH-Px)活性；丙二醛（MDA）含量及血清肌酸磷酸激酶（CPK）活性。电镜检查心肌细胞超微结构的改变。结果：腹腔注射Dox 48h后可致小鼠心肌明显损害，心肌SOD及Se-GSH-Px活性下降，MDA含量升高，血清中CPK的活性增强，同时出现心肌组织超微结构的损伤。GCs(62.5、125.0、250.0mg/kg）能增加心肌SOD、Se-GSH-Px活性，降低MDA含量，减少CPK释放，减轻心肌超微结构的损伤。结论：肉苁蓉总苷对阿霉素所致心肌损害有一定的保护作用，其机制可能与其保护心肌SOD及Se-GSH-Px活性及其清除自由基，防止脂质过氧化有关。     

硫氮(艹卓)酮对心肌钙反常损伤的影响

本实验建立心肌钙反常损伤模型,观察钙通道阻滞剂硫氮(艹卓)酮对心肌钙反常损伤的影响。发现硫氮(艹卓)酮能显著减轻心肌挛缩,提高冠脉流量和冠脉流出液中超氧化物歧化酶(SOD)活性,降低心肌细胞内的 CPK 释放及心室肌组织钙含量。实验结果表明,硫氮(艹卓)酮对心肌钙反常损伤有明显的保护作用。     

Use of an in Vitro Model for the Assessment of Muscle Damage from Intramuscular Injections: in Vitro-in Vivo Correlation and Predictability with Mixed Solvent Systems

The potential of binary mixtures of propylene glycol–water, ethanol–water, and polyethylene glycol 400–water to cause skeletal muscle damage (myotoxicity) following intramuscular injection was examined with an in vitro model using the isolated rat muscle. At moderate concentrations (20–40%, v/v) of the organic cosolvent, the order of myotoxicity was propylene glycol > ethanol polyethylene glycol 400. The in vitro results were then compared with in vivo toxicity in rabbits after injection of normal saline, 40% (v/v) polyethylene glycol 400, 40% (v/v) propylene glycol, indocyanine green in normal saline, and indocyanine green in 40% (v/v) propylene glycol. Employing the area under the creatine kinase activity curve from 0 to 72 hr as the index of skeletal muscle damage, an excellent in vitro–in vivo correlation was observed. The basic myotoxicity relationships obtained from the binary cosolvent systems were then used to examine the myotoxicity of ternary organic cosolvent mixtures. Several mixed solvent systems with the same theoretical molar solubilization power for a model compound, diazepam, were selected to determine (1) if myotoxicity can be reduced by changing the composition of the ternary mixtures and (2) if myotoxicity of the individual components is additive. For the solvent systems containing propylene glycol, ethanol, and water, the total myotoxicity equaled the sum of the individual myotoxicity of each component. In contrast, for the solvent systems containing polyethylene glycol 400, the total myotoxicity was only half of the sum of individual toxicities. These results suggest that polyethylene glycol 400 in mixed cosolvent systems might have a protective effect on the myotoxicity generated by intramuscular injections.     

Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral white matter at 1.5 T

Several studies have investigated the T1 and T2 relaxation time of choline, creatine and N-acetyl aspartate in cerebral white matter in normal human subjects. However, these studies demonstrate a large variation in T1 and T2 values. In the present study, relaxation times of choline, creatine and N-acetyl aspartate were determined in cerebral white matter in 15 control subjects (age 21 +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively.     

Metabolic profile of the hippocampus of Zucker Diabetic Fatty rats assessed by in vivo 1H magnetic resonance spectroscopy

Localized in vivo 1H magnetic resonance spectroscopy (MRS) was used to investigate metabolite levels in the brain of adult Zucker Diabetic Fatty (ZDF) rats, an animal model for type 2 diabetes mellitus. This study focussed on the hippocampus, assumed to be one of the main brain areas affected by this disease. Together with an almost 5-fold increase in blood glucose concentration measured by glucose oxidation, significant increases were found in the hippocampal concentrations of glucose (4.93 vs 1.66 mM p < 0.001), myo-inositol (6.52 vs 4.30 mM; p < 0.05), and total creatine (12.71 vs 10.50 mM; p < 0.05) in ZDF rats (n = 5) compared with littermates (n = 5). Although no obvious alterations were detected in the hippocampal levels of other metabolites, including NAA + NAAG and choline-containing compounds in the ZDF rats, the increase in Glc and Ins levels is in line with elevated brain tissue contents of these metabolites in patients with diabetes mellitus.