IL-1α及与IL-11、LIF和GDNF联合诱导胚鼠皮质、中脑神经干细胞向多巴胺神经元分化的比较

为比较皮质和中脑来源的神经干细胞(NSCs)定向分化为多巴胺神经元的情况,应用无血清和单克隆培养技术,分别从皮质和中脑组织中分离克隆、扩增NSCs,然后分成3组诱导分化:①对照组用10%胎牛血清诱导分化;②IL-1α组在10%胎牛血清的基础上加IL-1α诱导分化;③联合因子组在10%胎牛血清的基础上加IL-1α、IL-11、LIF及GDNF进行诱导分化。用酪氨酸羟化酶(TH)免疫组化染色检测多巴胺神经元。在100倍镜下随机取5个视野,计数每个视野中的TH阳性神经元数;并用图像分析软件处理TH阳性神经元的胞体面积和细胞周长;用STATA7.0统计软件进行统计处理。结果显示,皮质对照组中仅见极少的TH阳性神经元(0.25±0.163),中脑对照组中见少量TH阳性神经元(2±0.378);而皮质IL-1α组有较多的TH阳性神经元(15.5±0.866),中脑IL-1α组中的TH阳性神经元则为皮质IL-1α组的150%(22.875±1.517);皮质联合因子组中的TH阳性神经元数(25.75±0.940)与中脑联合因子组中的TH阳性神经元数(28.875±2.125)接近,无显著差异。胞体面积和细胞周长的结果显示出IL-1α组和联合因子组大于对照组、而联合因子组又优于IL-1α组的趋势。上述结果提示,中脑来源的NSCs本身具有一定的分化为多巴胺神经元的区域特异性,而皮质来源的NSCs在IL-1α、IL-11、LIF及GDNF等细胞因子的诱导下可改变其区域特异性而分化为较多较为成熟的多巴胺神经元。     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients.

Lymphokine-activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC), spleen cells (SPC) and regional lymph node cells (LNC) with IL-2 for 4 days were examined for their functional capabilities in 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC, although there was no difference between PBMC or SPC. The induction of mRNA of interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) and the production of these cytokines in the non-adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+, CD56+, and CD57+ cells in LNC either before or after culture, although OKIa1+ and CD25+ cells were uniformly increased in all cell populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL-2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma.     

树鼩脑缺血后适应升高海马区rCBF及VEGF的变化

目的 探讨缺血后适应(PC)缓解海马rCBF与血管内皮生长因子(VEGF)的变化及其机制.方法 建立树鼩血栓性局部脑缺血模型,通过激光多普勒血流计测量海马CA1区rCBF含量;用免疫组化法测定海马VEGF的表达.结果 树鼩脑缺血时海马rCBF逐渐降低,以24 h的改变最显著,脑缺血后海马CA1区VEGF阳性细胞数增多,12 h表达最强(P<0.01);缺血PC可显著影响缺血所致的改变:rCBF逐渐增加,72 h最显著(P<0.01),与此同时VEGF的表达除8 h外均比血栓性缺血组增强(P<0.01),12 h组最明显;电镜显示缺血24 h血栓性缺血组的海马线粒体应激及内质网池形成最明显,给予PC后得以缓解.结论 缺血12 h内PC通过明显增强VEGF的表达可能与其改善rCBF有关,从而延长治疗的时间窗.     

Peroxisomal fatty acid oxidation capacity is more resistant to ischaemic and reperfusion injury than mitochondrial fatty acid oxidation capacity in feline hearts

We investigated ischaemic and postischaemic mitochondrial and peroxisomal fatty acid oxidation capacity, ATP levels and regional function in 40 anaesthetized open chest cats subjected to 10 or 40 min of regional myocardial ischaemia with or without 3 h of reperfusion (n=10 in each situation). Following 10 min of ischaemia, the mitochondrial fatty acid oxidation capacity measured in tissue extracts from ischaemic tissue (nmol min^-1 mg protein^-1) was reduced in both subepi- and subendocardium, but was normalized in reperfused tissue extracts from both wall layers (0.29±0.03 and 0.30±0.04 vs. 0.57±0.05 and 0.59±0.05, P<0.05). Peroxisomal fatty acid oxidation capacity in tissue extracts was unaffected by ischaemia and reperfusion. ATP levels and regional function measured in the LAD region was partly restored transmurally. After 40 min of LAD occlusion, mitochondrial fatty acid oxidation capacity was reduced, with higher activity in subepi- than in subendocardium (0.27±0.05 vs. 0.19±0.04, P<0.05). Reperfusion did not restore mitochondrial fatty acid oxidation capacity. Peroxisomal fatty acid oxidation capacity was increased in the ischaemic subendocardium compared with levels in non-ischaemic subendocardium (0.53±0.02 vs. 0.45±0.03, P<0.05), with normalization at the end of reperfusion. ATP levels were non-uniformly reduced during ischaemia and not repleted during reperfusion. Regional function recovered in circumferential segments but not in longitudinal segments following 40 min of ischaemia. In conclusion fatty acid oxidation enzymes seem to be more resistant to ischaemia in peroxisomes than in mitochondria. Mitochondrial fatty acid oxidation is fully reversible following shortlasting ischaemia, but remains depressed following prolonged ischaemia and reperfusion.     

Functional neuroanatomy of human sleep states after zolpidem and placebo: a H215O-PET study

Changes in the functional organization of the brain during the course of sleep and waking are reflected by different patterns of regional cerebral blood flow (rCBF). To investigate the effect of the hypnotic zolpidem, a benzodiazepine receptor agonist, drug or placebo were administered to eight young, healthy men prior to bedtime. The subjects were sleep-deprived to promote sleep during the 4-h recording period in the positron emission tomography scanner. Intravenous injections of labelled water were administered during pre-drug wakefulness, and during Stage 2, Stage 4 and rapid eye movement (REM) sleep, each injection being followed by an emission scan. Statistical parametric mapping was used to investigate the effects of treatment and sleep states. During sleep (combined Stages 2 and 4, and REM sleep) relative rCBF was lower after zolpidem than after placebo in the basal ganglia and insula, and higher in the parietal cortex. A 'multiple study' analysis of REM sleep revealed that rCBF in the anterior cingulum was lower after zolpidem than after placebo, whereas rCBF in the occipital and parietal cortex, parahippocampal gyrus and cerebellum was higher. When the pooled data (drug and placebo) of Stages 2 and 4 were compared with wakefulness, rCBF was lower in prefrontal cortex and insula, and higher in the occipital and parietal cortex. The results indicate that some differences in rCBF from wakefulness to non-REM sleep are further augmented by zolpidem.     

Regional redistribution of blood in unanesthetized rats after blood loss

Relative changes in local blood volume in 46 vascular regions of the body after moderate and severe blood loss are described. Moderate blood loss caused a redistribution of blood from the skin of the chest and hind limbs, most organs of the abdomen and pelvis, the muscular and bony tissues of the abdomen, pelvis, and limbs to the brain, heart, lungs, kidneys, stomach and to the muscles of the head and neck. After severe blood loss the changes were similar but the blood volume in the kidneys and stomach was reduced; a relative increase in the blood volume in the muscular and bony tissues of the thorax also was observed. The intensity of the redistributive response to severe blood loss was less than to a moderate blood loss.Central Research Laboratory, S. M. Kirov Leningrad Postgraduate Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR P. N. Veselkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1045–1047, September, 1976.     

Effect of Transmural Pressure on Constrictor Reactions of Caudal Artery in Hypotensive and Hypertensive Rats

Clipping of the abdominal aorta distally to the renal arteries produces a persistent decrease in blood pressure in hindquarter vessels by 35-40%. On week 6-7 postoperation, the reactions of the caudal artery perfused in vitro under constant pressure to norepinephrine were studied. At transmural pressure of 150 mm Hg, the vascular responses in hypotensive rats were reduced compared to those in normotensive control. By contrast, the responses of hypertensive vessels were more pronounced at 75 mm Hg even after deendothelization.     

The effects of nisoldipine alone and in combination with beta-adrenoceptor blockade on systemic haemodynamics and myocardial performance in conscious pigs

The peak effects of 10 mg nisoldipine p.o. with or without 80mg propranolol p.o. on systemic and regional haemodynamics inconscious pigs were investigated. Nisoldipine increased heartrate (70%), cardiac output (67%) and maxLVdP/dt (75%), but decreasedmean arterial pressure (21%) as systemic vascular conductanceincreased by 120%. Left ventricular systolic and end-diastolicpressures were not affected. Vasodilatation occurred in mostorgans. The increase in left ventricular blood flow (150%) favouredthe epicardial (195%) over the endocardial (110%) layers. Asa result the endo–epi blood flow ratio decreased by 30% When nisoldipine was administered simultaneously with propranolol,heart rate (29%), cardiac output (35%) and systemic vascularconductance (65%) increased, but maxL VdP/dt did not change.Mean arterial (18%) and left ventricular systolic (10%) pressuredecreased; left ventricular end-diastolic pressure was againunaffected. In most organs vasodilatation was attenuated, butstill present, compared to the changes after nisoldipine alone.The increase in epicardial blood flow (70%) again exceeded thatin endocardial blood flow (35%), however, the endo–epiratio decreased by only 15%. In the presence of propranolol,nisoldipine did not exert a negative inotropic action whilethe reflex-tachycardia was attenuated. In addition, no detrimentaleffects on perfusion of regional vascular beds were observed.     

Arterial hypertension associated with the use of a tourniquet with either general or regional anaesthesia

A hypertensive patient with left cardiac enlargement developed marked hypertension under general anaesthesia, during which time a tourniquet was applied around his thigh. When the tourniquet was released, severe hypotension ensued which responded to therapy. The patient, however, died 16 h later of a myocardial infarction. Because of this incident, the anaesthetic and haemodynamic data of 699 patients who underwent limb surgery with a pneumatic tourniquet inflated for at least an hour were retrospectively examined using multivariate analysis. A 30% increase in systolic and/or diastolic arterial blood pressure occurred in 27% of the total patient material and in 67% of those who had had a general anaesthetic. There was a higher frequency of the occurrence of "tourniquet hypertension" with older age, longer operations and the operation site being the lower rather than the upper limb. Tourniquet hypertension rarely occurred in patients with spinal anaesthesia (2.7%) and brachial plexus blockade (2.5%), while those with intravenous regional anesthesia had a higher incidence (19%) of hypertension.