钙调神经磷酸酶参与心衰患者心肌重构的信号转导

目的：探讨血管紧张素Ⅱ(Ang Ⅱ)介导的钙调神经磷酸酶（CaN）信号通路参与心力衰竭（CHF）患者心肌重塑的机制。方法:选择因瓣膜性心脏病接受二尖瓣置换术的CHF病人39例，正常对照38例(其中8例来自意外伤亡的器官捐献者)。彩色多普勒超声心动图仪检测心脏扩大和心功能参数。放免法检测血浆及心肌组织Ang Ⅱ浓度，免疫沉淀法测心肌组织CaN、活化T细胞核因子(NFAT₃）、锌指转录因子(GATA₄)磷酸化及蛋白表达，RT-PCR检测肌球蛋白重链（β-MHC）mRNA表达。结果:AngⅡ分别与心脏扩大参数呈显著正相关，而与心功能参数呈显著负相关。CHF患者心肌组织CaN蛋白表达、CaN磷酸化、GATA^₄蛋白表达及β-MHC mRNA表达明显高于对照组，随心功能恶化其表达逐渐增加；NFAT₃磷酸化随心功能恶化而减弱。结论：肾素血管紧张素系统（RAS）激活的CaN信号通路在CHF患者心肌重构机制中可能起重要作用。     

Recovery of hypertrophied rat hearts after global ischemia and reperfusion at different perfusion pressures

The ability to resist transient ischemia was studied in isolated hearts of 18 months old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Both types of hearts showed optimal performance during the preischemic period when perfused at a diastolic perfusion pressure of 8.0 (WKY) and 13.3 (SHR) kPa. Hemodynamic recovery of WKY hearts during reperfusion at 8.0 kPa, following 45 min global ischemia, was satisfactory. Coronary perfusion completely normalized, contractility (dP _lv/dt _max) was slightly depressed and cardiac output returned, on the average, to 40% of the preischemic values. In contrast, hemodynamic function of SHR hearts reperfused at 13.3 kPa was greatly depressed, as evidenced by almost complete abolition of cardiac output, severe reduction ofdP _lv/dt _max and persistent underperfusion of the endocardial layers. In addition, the postischemic release of lactate dehydrogenase was retarded and enhanced. The release patterns of degradation products of adenine nucleotides showed a shift to the endstage produets xanthine and uric acid. The enhanced vulnerability of the hypertrophied heart to ischemia was even more expressed when the SHR hearts were reperfused at 8.0 kPa. Postischemic function was characterized by electrical instability, loss of contractility and cardiac output, and noreflow in the endocardial layers. Persistent accumulation of lactate and degradation products of adenine nucleotides in the postischemic hearts are in line with the lack of reperfusion. The present results indicate that a detailed mechanistic explanation for the reduced ability to withstand ischemia of SHR cannot be based on differences in ATP content or an altered anaerobic glycolitic activity prior and during ischemia. It is suggested that a defect on the circulatory level, probably caused by enhanced reactivity of the coronary vessels towards ischemia-elicited factors, is responsible for the higher vulnerability of hypertrophied heart to an ischemia insult.Supported by Medigon/NWO (grant number 900516091)     

高雌激素血症对雌性心肌梗塞大鼠心肌舒缩性能的影响

本文研究了高雌激素血症对雌性心肌梗塞(MI)大鼠心肌舒缩性能的影响。结果:(1)MI组血浆雌二醇(E_2)先略升高而后降低,雌二醇处理MI组(MIE_2)血浆雌二醇明显升高。(2)MIE_2组心肌纤维直径比对照假手术组(CS)及MI组显著增大(10.65±0.59 VS 7.65±0.40及10.15±0.54gm,P<0.001,<0.02)。(3)两MI组的LVSP、±dp/dt max均显著降低,T-值明显延长,尤以MIE_2组更为显著(10.5±4.1 VS 6.2±4.6ms,P<0.02)。(4)两MI组动脉压显著降低,HR减慢,LVET延长;在9天观测点,MIE_2组的HR仍较MI组显著减慢、LVET明显延长。提示高雌激素血症可使雌性心肌梗塞大鼠心肌舒缩性能降低。     

Evaluation of the Antioxidant Effects of Ziziphus Mauritiana Lam. Leaf Extracts Against Chronic Ethanol-Induced Hepatotoxicity in Rat Liver

Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1ml/100g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.     

Microphotometric investigation of oxidative enzyme activity in endometrial epithelium of rats after ovariectomy and injection of testosterone propionate

Activity of oxidative enzymes in the epithelium lining the uterine cavity and in the glandular epithelium of ovariectomized rats in the period of climacteric disorders was investigated by a comparative microphotometric method. An increase in lactate dehydrogenase (LD) and glucose-6-phosphate dehydrogenase (G6PD) activity and a decrease in succinate dehydrogenase (SD) and NAD- and NADP-diaphorase activity were found in the epithelial cells lining the uterine cavity. LD activity was increased in the glandular epithelium but SD, and NAD- and NADP-diaphorase activity was sharply reduced. Injection of testosterone propionate caused a marked increase in the activity of the oxidative enzymes studied in the endometrial epithelium of the rats compared with their activity in control rats and in rats not receiving the hormone.Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. Department of Obstetrics and Gynecology, Daghestan Medical Institute, Makhachkala. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 209–212, February, 1978.     

Effects of training at simulated altitude on performance and muscle metabolic capacity in competitive road cyclists

Summary Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3–4 weeks, 4–5 sessions/week, each session consisting of cycling for 60–90 min continuously and 45–60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr=2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle.     

Myokardiale Aufnahme von Lidocain,Mexiletin und Amiodaron nach Akutapplikation

Summary To assess acute myocardial uptake of antiarrhythmic drugs, we measured drug concentrations simultaneously in the aorta and in the coronary sinus during diagnostic cardiac catheterization. Measurements were taken 1, 2, 3, 4, 5, 7, and 10 minutes after intravenous bolus application of lidocaine (n= 10, 25 mg), mexiletine (n= 5, 25 mg andn= 10, 100 mg), or amiodarone (n= 10, 25 mg). Drug levels were measured by high-pressure liquid chromatography. Maximal concentrations were observed after 2–5 min. After 3–5 min coronary sinus levels exceeded aorta levels, indicating the end of net myocardial drug uptake. In contrast to lidocaine and amiodarone, no mexiletine was found in the coronary sinus 15 s after the end of drug application, obviously indicating a high myocardial drug content. Furthermore, the data provide an explanation for the acute efficacy of amiodarone. The myocardial uptake may result in various pharmacodynamic effects of antiarrhythmic drugs.

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deAbkürzungen Art. Arteria - min Minuten - s Sekunden - i.v. intravenös Mit Unterstützung der Deutschen Forschungsgemeinschaft (Ni 241/1–2)     

Plasmid-specified aminoglycoside-modifying enzymes in clinical isolates of Klebsiella pneumoniae

In 106 clinical isolates of multiresistant Klebsiella pneumoniae strains, we found that aminoglycoside-resistance was due mostly to two adenylating enzymes: AAD (2) (56.6%), that modifies gentamicin, kanamycin, tobramycin and sissomicin, and AAD (3) 9 (56.6% + 19.8%) that modifies streptomycin and spectinomycin. The identification of these enzymes was possible by MICs determination against a set of aminoalycosides antibiotics. AAD (2) + AAD (3) 9 were coded by conjugative plasmid of about 120 Md.     

Early biochemical and morphological changes of the rat adrenal medulla induced by xylitol

Long-term administration of high doses of xylitol and other polyols in rats has been associated with an increase in adrenal medullary hyperplasia and neoplasia. In order to exclude age-related factors and to differentiate between unspecific stress reactions and direct effects of the compound administered, a model was developed for quantifying early adrenomedullary responses. Male SD rats were fed xylitol (10% or 20% in the diet) for 2 and 8 weeks, and early biochemical changes were correlated with a stereological analysis of the adrenal medulla. At first, the in vivo rate of catecholamine (CA) biosynthesis was slightly decreased (at 2 weeks). This was followed by an increase in dopamine--hydroxylase (DBH) activity (at 8 weeks). By that time, the total chromaffin cell volume had increased and the number of chromaffin cells per reference volume had decreased in a dose-dependent way. The total number of chromaffin cells per adrenal gland showed a distinct tendency towards an increase. Adrenal epinephrine and norepinephrine contents were not altered, and both tyrosine hydroxylase and phenylethanolamine-N-methyltransferase activities remained unchanged. These data suggest that continued xylitol administration evoked an inhibitory effect on CA synthesis that, together with stimulation of the adrenal medulla brought about by the compound, resulted in compensatory medullary hypertrophy and hyperplasia.