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。     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Cardiac metabolism: A technical spectrum of modalities including positron emission tomography,single-photon emission computed tomography,and magnetic resonance spectroscopy

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively,³¹P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with¹⁸F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by¹¹C-labeled acetate PET may prove to be more accurate than¹⁸F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are¹²³I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-¹²³I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with³¹P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.     

Thoracic epidural analgesia in aortocoronary bypass surgery II: effects on the endocrine metabolic response

Thoracic epidural analgesia (TEA) may offer haemodynamic benefits for patients with coronary heart disease going through major surgery. This may – in part – be secondary to an effect on the endocrine and metabolic response to surgery. We therefore investigated the effect of TEA on the endocrine metabolic response to aortocoronary bypass surgery (ACBS).
Thirty male patients (age < 65 years, ejection fraction > 0.5) were randomized into 3 groups; the HF group receiving a high dose fentanyl (55 μg–kg^-1) anaesthesia, the HF + TEA group with the same fentanyl dose + TEA with 10 ml bupivacain 5 mg ml^-1, followed by 4 ml every hour, and the LF + TEA group receiving fentanyl 15 μg kg^-1 + TEA. Adrenalin, noradrenalin, systemic vascular resistance (SVR), glucose, Cortisol, lactate and free fatty acids were followed during the operation and for 20 h postoperatively.
A significant increase in adrenalin, noradrenalin and SVR was found in the HF group whereas this increase was blocked in both epidural groups. An increase in glucose and Cortisol was noticed in all groups, but the increase was delayed in the epidural groups.
Our results suggest that a more effective blockade of the stress response during ACBS is obtained when TEA is added to general anaesthesia than with high dose fentanyl anaesthesia alone.     

Acute toxicity of two pyrethroids,permethrin, and cypermethrin in neonatal and adult rats

The present study aims specifically at obtaining a comparison of the acute toxicity of cypermethrin (CY), a type I pyrethroid, and permethrin (PERM), a type II pyrethroid, administered orally as a single dose to neonatal and adult rats, and at assessing the importance of pyrethroid biotransformation in CY and PERM toxicity through use of drug metabolism inhibitors. Our experiments show that CY is more toxic than PERM to adult and neonatal rats. The sensitivity of neonatal rats both to CY and to PERM toxicity is higher, the younger the animals. CY is much more toxic than PERM in the neonatal rat, compared with the adult. In rats aged 8, 16, and 21 days, pretreatment with piperonil butoxide (PB), a monooxygenase inhibitor, or with tri-o-tolyl phosphate (TOTP), an esterase inhibitor, does not produce significant variations in the lethal effects of CY and PERM. Instead, in the adult rats, a significant increase in CY (X²=5.97;p<0.05) and PERM (X²=4.37;p<0.05) mortality occurred in rats pretreated with esterase inhibitors, whereas no increase in CY and PERM toxicity was found in adult animals pretreated with monooxygenase inhibitor. It was concluded that the higher level of sensitivity of the neonate rat to pyrethroid toxicity is probably due to incomplete development of the enzymes which catalyze the metabolism of pyrethroids in the liver of young animals. It is suggested that ester hydrolysis is an important pyrethroids detoxification reaction in the adult rat.     

低剂量激素替代治疗对绝经后妇女骨代谢的影响

目的 探讨低剂量结合型雌激素（ＣＥ）和安宫黄体酮（ＭＰＡ）联合应用对骨代谢的影响，方法３４例绝经后妇女随机分为两组，试验组１７例，ＣＥ０．６２５ｍｇ与ＭＰＡ２ｍｇ隔日口服交替应用，对照组１７例，口服ＣＤ０．６２５ｍｇ／ｄ，每月连续服用２５ｄ，后１０ｄ加用ＭＰＡ４ｍｇ。两组均连续服用４周期，于用药前后分别测定血碱性磷酸酶（ＡＬＰ）及尿Ｃａ／Ｃｒ比值。结果 实验组完成治疗者１６例，对照组完成治疗者１５