Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.     

急性颅脑损伤患者脑脊液中兴奋性和抑制性氨基酸含量改变及其临床意义

采用氨基酸自动分析仪检测了１８例急性颅脑损伤患者脑脊液中谷氨酸、天门冬氨酸、牛磺酸、甘氨酸、丙氨酸、γ－氨基丁酸、脯氨酸含量的动态变化。结果发现，伤情越重、预后越差的患者，脑脊液中牛磺酸、γ－氨基丁酸、丙氨酸含量伤后早期升高越明显，恢复至正常的时间也越长；其中２例早期死于急性弥漫性脑肿胀、脑水肿的患者，伤后当天脑脊液中牛磺酸含量分别为９２．６和５１．５μｍｏｌ／Ｌ，是对照值的９．６倍和５．４倍，γ－氨基丁酸含量分别为１１９．８和２４６．２μｍｏｌ／Ｌ，是对照值的２．７倍和５．５倍。表明伤后脑脊液中牛磺酸、γ－氨基丁酸和丙氨酸含量的动态变化可初步反映颅脑损伤的严重程度及颅脑损伤患者的脑功能恢复状况，并可能与急性脑水肿、脑肿胀的病理生理过程有关。     

Protective Effect of Tetrandrine against Excitatory Amino Acids induced Neuronal Injury in Cortical Culture

兴奋性氨基酸类神经毒剂与粉防己碱（ｔｅｔｒａｎｄｒｉｎｅ，Ｔｅｔ）共同作用于原代培养胎鼠大脑皮层神经元２４小时，发现１０７，１０６ｍｏｌ·Ｌ１Ｔｅｔ明显降低５０μｍｏｌ·Ｌ１谷氨酸（ｇｌｕｔａｍａｔｅ，Ｇｌｕ），３００μｍｏｌ·Ｌ１βＮｍｅｔｈｙｌａｍｉｎｏＬａｌａｎｉｎｅ（ＢＭＡＡ，ＮＭＤＡ受体激动剂）和２０μｍｏｌ·Ｌ１βＮｏｘａｌｙｌａｍｉｎｏＬａｌａｎｉｎｅ（ＢＯＡＡ，ｎｏｎＮＭＤＡ受体激动剂）导致的培养液乳酸脱氢酶（ｌａｃｔａｔｅｄｅｈｙｄｒｏｇｅｎａｓｅ，ＬＤＨ）活性的增高；细胞形态损害减轻，细胞数量增加。对２０μｍｏｌ·Ｌ１ＮＭＤＡ介导的神经元损伤改变无影响。提示Ｔｅｔ对某些Ｇｌｕ类神经毒剂引起的胎鼠大脑皮层神经元损伤有一定保护作用，其机制可能是抑制细胞膜上的Ｎａ＋通道开放，阻止膜去极化而影响电压依赖性Ｃａ２＋通道启动。对ＮＭＤＡ受体可能亦有一定作用。     

易善复加丹参治疗病毒性肝炎合并脂肪肝疗效观察

目的　评价易善复加丹参在病毒性肝炎合并脂肪肝的临床疗效。方法　选择病毒性肝炎合并脂肪肝 98例 ,随机分成治疗组和对照组 ,治疗组 68例 ,应用易善复加丹参治疗 ,疗程 3个月。结果　治疗组血脂 (TC、TG)、肝功能 (ALT、γ -GT)、B超脂肪肝图象及临床症状等项目的改善均明显优于对照组 (P <0 .0 1～ 0 .0 5) ,且无明显副作用。结论　易善复加丹参治疗病毒性肝炎合并脂肪肝对促进肝脏脂肪代谢、降低血脂、修复损伤的肝细胞 ,且阻止或改善肝纤维化均有明显的功效     

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.     

Extracellular adenosine,formed during low level NMDA receptor activation,provides an inhibitory threshold against further NMDA receptor-midiated neurotransmission in the cortex

In the cortex only a few of the available NMDA receptors must be activated to evoke maximal release of adenosine. In fact, maximal adenosine release occurs at 30 μM NMDA, a concentration at which noradrenaline release is only 20% maximal. NMDA-evoked noradrenaline release appears to require the generation of propagated action potentials, while adenosine release does not. Noncompetitive block of NMDA-evoked release of adenosine, but not noradrenaline, can be overcome by increasing NMDA concentrations. The above findings are consistent with the possibility that there are spare receptors for NMDA-evoked adenosine release, but not for nor-adrenaline release. These spare receptors are not due to elevated levels of glycine in the vicinity of those NMDA receptors mediating adenosine release. Functionally, it appears that low level NMDA receptor activation provides a purinergic inhibitory threshold against higher level NMDA receptor mediated processes. This could provide inhibitory tone and selectivity for critical functions, such as learning, memory, and synaptic plasticity in the cortex. © 1993 Wiley-Liss, Inc.     

反相高压液相色谱法测定血清中部分氨基酸

目的：建立测定血清中精氨酸含量的方法。方法：反相高压液相色谱法。ＨｙｐｅｒｓｉｌＢＤＳ柱，邻苯二甲醛柱前衍生化、萤光检测法检测。结果：精氨酸线性范围为３８３μｍｏｌ／Ｌ～４７８９μｍｏｌ／Ｌ，８种氨基酸的最低检测限为２μｍｏｌ／Ｌ，日内变异系数为２７５％～１１９３％，日间变异系数为７０５％～１２３９％，５种氨基酸的回收率为９６３３％～１００７８％。正常人血清精氨酸水平为９２７７±１７９０μｍｏｌ／Ｌ，糖尿病患者血清精氨酸水平则为７８６１±３３０３μｍｏｌ／Ｌ（Ｐ＞００５）。结论：本方法简单易行，方法学实验结果满意，适用于临床测定相关氨基酸的需要     

Determination of the ratios of the aromatic amino acid residues by first- or second-derivative UV spectrometry for a simple characterization of peptides

A method for the simultaneous determination of the ratios of the three aromatic amino-acid residues in peptides was set up in acidic conditions. Binary and ternary mixtures of these amino acids were prepared, and first- and second-derivative spectra then calculated from their 0.1 nm resolution spectra between 240 and 320 nm. Certain spectral bands were chosen to differentiate tyrosine from tryptophan on the first-derivative spectra, and phenylalanine from tyrosine and tryptophan on the second-derivative spectra. Variation of the amplitude of the chosen bands was shown to be a linear function of the ratio of the aromatic amino acids in the mixture. This technique was validated with peptides whose sequence was known. The difference between theoretical and experimentally determined ratios was lower than 10%. Since the results are obtained as ratios, neither the concentration nor the nature of the peptide has to be known. The feasibility of application using a photodiode array detector with high resolution in reversed-phase high-performance liquid chromatography is discussed. © Munksgaard 1995.     

Infant rat separation is a sensitive test for novel anxiolytics

1. Rat pups emit ultrasonic calls during brief episodes of social separation. These calls have been variously described as “distress” calls and may be related to the separation cries expressed by the young of many mammalian species.

2. Ultrasonic call of rat pups are modulated by environmental stimuli such as ambient temperature, olfactory and tactile stimuli associated with the nest.

3. Calls are also sensitive to a variety of purported anxiolytic and anxiogenic drugs, including the benzodiazepines, serotonin agonists, and ligands at the NMDA-glycine receptor complex.

4. In addition to providing a simple test for the anxiolytic properties of drugs, this model may also provide new insights about the development and neurobiology of anxiety.     

Synopses of Posters Presented at the International Workshop on Brain Uptake and Utilization of Fatty Acids,Lipids, and Lipoproteins: Application to Neurological Disorders

Thirty-five posters were presented at the Workshop on Brain Uptake And Utilization Of Fatty Acids, Lipids, and Lipoproteins. They were grouped into four categories: (1) mechanisms of lipid uptake and transport to the brain, (2) lipoproteins and polyunsaturated fatty acids, (3) eicosanoids in brain function, and (4) fatty acids and lipids in brain disorders. This article summarizes the highlights of the research presented in these posters. The individual abstracts follow these synopses.