Scopolamine abolishes cerebral blood flow response to somatosensory stimulation in anesthetized cats: PET study

The effect of the cholinergic blocker, scopolamine on the cerebral blood flow (CBF) response to vibrotactile stimulation of a fore paw was studied using high-resolution positron emission tomography and H₂¹⁵O in 5 pentobarbital-anesthetized cats. Before scopolamine injection, the CBF response to the stimulation was found in the contralateral somatosensory cortex (mean ratio (contralateral/ipsilateral) control: stimulated1.02 ± 0.02: 1.17 ± 0.05; P < 0.01). After intravenous injection of scopolamine (0.35 mg/kg), the CBF response was abolished. However, the cerebral metabolic rate of glucose (CMRGlu) response to the same stimulation was unchanged after scopolamine injection in the same cats. We concluded that scopolamine abolishes the CBF response but not neuronal response to stimulation. We suggest that cholinergic mechanisms may play an important role for mediating CBF coupling to neuronal activity during physiological stimulation.     

维生素K4、维生素D2对绝经妇女骨折早期骨代谢的影响

为探讨不同剂量水平的维生素K4及维生素D对绝经妇女骨折早期骨代谢的影响。选择年龄60~84岁(72.17±1.216岁),绝经女性骨折病人35例,随机分为4组,分别给予不同剂量的维生素K4及维生素D口服,实验进行20天。通过观察患者服药前后血清钙、血清磷、血清碱性磷酸酶、血清凝血酶原时间及血清骨钙素值的变化,综合评价维生素K、维生素D对老年妇女骨折早期骨代谢的影响。结果显示,不同剂量水平维生素K4、维生素D对绝经妇女骨折早期骨代谢的影响不同,有统计学意义。维生素K4对骨代谢的影响作用超过维生素D,并随剂量水平不同而差异有显著性。但维生素K4、维生素D对骨代谢的影响无交互作用。表明维生素D、维生素K4能促进骨折早期骨代谢,对骨折愈合有一定促进作用,且维生素K的作用强于维生素D。     

Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.     

Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat.

AIMS: Severe sustained bradycardia may cause acute and possibly chronic congestive heart failure (CHF). The aim of this study was to investigate acute and chronic effects of complete heart block (CHB) on cardiac function, morphology, and creatine (Cr) metabolism. METHODS AND RESULTS: CHB was induced in male Sprague-Dawley rats (approximately 250 g, n = 11) by means of electrocautery applied to the region of AV node and were compared with controls (n = 15). The rats were investigated at 1, 3, and 12 weeks after CHB induction with transthoracic echocardiography. Invasive haemodynamic assessment of left and right ventricular pressures was performed at 12 weeks. After the sacrifice, the hearts were freeze-clamped for analysis of myocardial Cr, and high energy phosphometabolites. The efficacy of operative procedure was 54%. The peri-operative mortality rate was 20%. Heart rate (HR) decreased by approximately 50% (P < 0.01) while stroke volume (SV) increased 2.5 times (P < 0.01) in the CHB rats. Cardiac index remained unchanged. The rats with CHB grew normally and were in no apparent distress. Filling pressures in left and right ventricles were normal. The CHB rats developed marked cardiomegaly with biventricular dilatation and eccentric left ventricular hypertrophy (P < 0.01). There was no change in the myocardial content of Cr and high energy phosphometabolites. CONCLUSION: Rats with CHB are compensating for reduction in HR with increased SV without haemodynamic and biochemical characteristics of CHF. This model may be useful to study the effects of CHB and bradycardia on myocardial structure, function, electrophysiology, and metabolism as well as for studies of cell therapy for reparation of AV conductance.     

母体钙代谢与补钙对妊娠的影响

妊娠期缺钙严重影响母婴的安全健康 ,其原因是由于妊娠期母体钙代谢发生变化 ,使母体血清游离钙离子浓度降低 ,血清铅浓度增高。有关研究表明 ,母体缺钙导致血铅竞争性过高 ,使胎儿身长、体重均小于胎龄儿 ,胎儿宫内发育迟缓的发生率增高 ,甚至发生早产、死胎等。同时发现血清钙离子可能对内源性一氧化氮合成释放起调节作用 ,而内皮素是最强的缩血管物质之一 ,母体补钙可调节一氧化氮与内皮素的平衡 ,从而降低妊高征的发生率。因此孕期补充钙剂是非常重要的。     

Renal acid excretion in early infancy

In early infancy, complex disorders of acid base metabolism are more frequent than in any other age group, with a predisposition to metabolic acidosis due to an age-related low renal capacity for acid excretion and an unphysiologically high actual renal acid load in nutrition with common formulas. Recently in preterm and small-for-gestational-age infants, persistent maximum renal net acid excretion (NAE) with subnormal or normal blood acid base status, impaired weight gain, and adaptive hormonal reactions have been observed. Incipient late metabolic acidosis is one example of a mixed disorder of acid base metabolism with maximum renal NAE in early infancy. Alkali therapy is highly effective and can be realized both on an individual basis, using urine pH screening as a diagnostic criterium for maximum renal acid stimulation, or on a general preventive level using modified standard formula with a reduced actual renal NAE similar to that seen on alimentation with human milk. From an integrated point of view, the low glomerular filtration rate and renal capacity for acid excretion beyond the developmental age of more than 44 weeks, may well be interpreted as the result of a specific adaptation to breast feeding sparing energy, and thus an evolutionary advantage for the survival of mother and child. Received July 10, 1996; received in revised form and accepted October 7, 1996     

Electron-autoradiographic investigation of viability of human cells after death. Postmortem activation of RNA synthesis in neutrophils

Department of Pathological Anatomy, A. V. Vishnevskii Institute of Surgery, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR D. S. Sarkisov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 2, pp. 199–201, February, 1991.     

-2-Hydroxyglutaric acid inhibits mitochondrial creatine kinase activity from cerebellum of developing rats

L-2-Hydroxyglutaric acid (LGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as L-2-hydroxyglutaric aciduria (LHGA). Although this disorder is predominantly characterized by severe neurological findings and pronounced cerebellum atrophy, the neurotoxic mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of LGA, at 0.25-5mM concentrations, on total creatine kinase (tCK) activity from cerebellum, cerebral cortex, cardiac muscle and skeletal muscle homogenates of 30-day-old Wistar rats. CK activity was measured also in the cytosolic (Cy-CK) and mitochondrial (Mi-CK) fractions from cerebellum. We verified that tCK activity was significantly inhibited by LGA in the cerebellum, but not in cerebral cortex, cardiac muscle and skeletal muscle. Furthermore, CK activity from the mitochondrial fraction was inhibited by LGA, whereas that from the cytosolic fraction of cerebellum was not affected by the acid. Kinetic studies revealed that the inhibitory effect of LGA on Mi-CK was non-competitive in relation to phosphocreatine. Finally, we verified that the inhibitory effect of LGA on tCK was fully prevented by pre-incubation of the homogenates with reduced glutathione (GSH), suggesting that this inhibition is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of creatine kinase activity for energy homeostasis, our results suggest that the selective inhibition of this enzyme activity by increased levels of LGA could be possibly related to the cerebellar degeneration characteristically found in patients affected by L-2-hydroxyglutaric aciduria.     

肝脏外科患者术后输注脂肪乳剂对蛋白质代谢的影响

将32例肝脏外科疾病患者随机分为Ⅰ组（单能源TPN组10例）；Ⅱ组（双能源TPN组11例，其中脂肪乳剂用量为1g·kg－1·d－1）；Ⅲ组（双能，TPN组11例，其中脂肪乳剂用量为2g·kg－1·d－1）。术后按组别给予TPN支持共6天，术前1天、术后第1和第6天测定肝功，糖代谢及蛋白质合成代谢指标。结果：①Ⅱ、Ⅲ组术后第6天肝脏酶学指标明显下降（P＜0．05），而Ⅰ组仍高于术前水平（P＜O．05）；②Ⅱ、Ⅲ组术后糖代谢基本恢复正常，而Ⅰ组出现高血糖症及高胰岛素血症（P＜0．05）；③Ⅱ组肝脏蛋白质合成水平恢复术前水平或略有提高（P＜0．05），而Ⅰ和Ⅲ组术后蛋白质合成功能仍低（P＜0．05）。结果提示：含脂肪乳剂的TPN支持对肝脏外科患者术后的肝功恢复有益，能促进蛋白质合成及肝细胞再生，并且在进行TPN支持时按1g·kg－1·d－1给予脂肪乳剂较为安全合理。