Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression

Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL- 6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline- treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.     

微囊化卵巢细胞植入卵巢摘除小鼠腹腔对胰岛α和β细胞生物活性的影响

目的:观察微囊化卵巢细胞种植于去卵巢小鼠腹腔后对胰岛细胞生物活性的影响。方法:实验于2005-06/2006-09在首都医科大学生殖医学研究中心完成。将30只成年雌性ICR小鼠随机分为3组,正常对照组、卵巢摘除组和微囊种植组,每组10只。卵巢摘除组经背部切口取出双侧卵巢;微囊种植组于卵巢摘除同时,将微囊化卵巢细胞种植到腹腔内。正常对照组于饲养第10天,卵巢摘除组和微囊种植组于术后60d处死采血并取出胰腺组织。以放射免疫法测定各组实验动物血清中雌二醇的质量浓度。胰腺组织分别应用免疫组织化学法标记胰高血糖素、胰岛素、胰岛素受体α和胰岛素受体底物2。实验结果用图像分析仪进行吸光度值的测定。结果:30只小鼠均进入结果分析。①卵巢摘除组血清雌二醇的质量浓度低于正常对照组、微囊移植组,差异有非常显著性意义[分别为(1.089±0.885),(37.582±20.019),(35.766±13.313)ng/L,t=5.759,8.219,P<0.01],正常对照组与微囊种植组之间差异无显著性意义。②卵巢摘除组胰高血糖素、胰岛素的阳性产物(A)显著高于正常对照组,差异有显著性意义(分别为1.282±0.076,1.038±0.053;1.023±0.055,0.822±0.090,P<0.01),微囊种植组与正常对照组比较差异无显著性意义;卵巢摘除组胰岛素受体α和胰岛素受体底物2的阳性产物(A)显著低于正常对照组,差异有显著性意义(分别为0.929±0.142,1.099±0.098;0.891±0.118,1.135±0.069,P<0.01),微囊种植组与正常对照组比较差异无显著性意义。结论:在去除卵巢的同时进行了微囊化卵巢细胞的种植,可明显提高血清雌二醇的质量浓度,较有效地调节胰岛α细胞和β细胞的生物活性。     

8The effect of food on electrical and mechanical activity of the canine antrum

Cyclic vomiting syndrome (CVS) is an unexplained disorder characterized by recurrent attacks of nausea and vomiting. The aim of this study was to investigate the characteristics of gastric myoelectrical activity in patients meeting Rome II criteria for CVS and studied between cycles using cutaneous electrogastrography (EGG). Methods: 11 patients (6M, 5F, mean age: 31 years, range: 16–60) with CVS (5 symptomatic and 6 asymptomatic at the time of the study) underwent EGG between acute CVS attacks. EGG recordings were made for 30 minutes in the fasting state and for 60 minutes after ingestion of a caloric liquid meal (Boost, 360 kcal). Power spectral analysis methods were used to extract quantitative EGG parameters: EGG dominant frequency/power, change in postprandial EGG power, percentages of normal slow waves (2 to 4 cpm) and dysrythmias including tachygastria (slow‐wave frequency >4 cpm) and bradygastria (slow‐wave frequency <2 cpm) in each recording session. Patients were asked to score their symptoms of nausea, vomiting and abdominal pain (0 = none, 4 = constant) during both pre‐ and postprandial periods. Data are expressed as mean ± SE. Results: 7/11 demonstrated an abnormal EGG (dysrhythmia >30% in 4 patients and a decrease in postprandial EGG power in 6 patients). 5/11 patients had symptoms (nausea) during EGG recording and all had an abnormal EGG. The major abnormalities of EGG were tachygastria and a decrease in EGG postprandial power change. In comparison with asymptomatic patients at the time of the study, symptomatic patients had significantly more tachgastria (20.4 ± 3.9% vs. 6.7 ± 2.7%, P = 0.01) and significantly less normal slow waves (67.6 ± 2.0% vs. 86.7 ± 2.8%, P < 0.05) in the fed state. The increase in EGG postptandial power in symptomatic patients was also significantly less than asymptomatic patients (­2.55 ± 1.01 dB vs. 1.14 ± 0.54 dB, P < 0.05). Conclusions: 1) Abnormalities of EGG are presented in CVS between acute episodes and could explain some of the symptoms present; 2) Abnormal gastric myoelectrical activity is part of the spectrum of the CVS patients.     

Frontal lobe activation during word generation studied by functional MRI

Aims – To further delimit the specific verbal operations occurring in the dorsolateral frontal cortex during the generation of words, methods – different verbal fluency tasks guided by distinct specifications (phonological, semantic, or automatic production of words) were used in a functional magnetic resonance study. The study group comprised 10 right-handed normal subjects ranging in age from 23 to 27 years. Functional magnetic resonance images were obtained in a 1.5-Tesla magnet using a spoiled GRASS sequence. Results – Noticeable activation was found during the word generation tasks in the dorsolateral frontal cortex. The region showing the most prominent activation was the posterior part of the left middle frontal gyrus. Nevertheless, the different tasks each had a different activation effect. The phonologically guided generation of words produced the most consistent activation of the middle frontal gyrus, which mainly involved the premotor cortex. Conclusion – The results suggest that operations concerned with the generation of sound sequences, rather than the amount of produced words or their semantics, are responsible for sustained focal activity observed in the frontal lobes during verbal fluency tasks.     

Effects of nitric oxide and sodium nitroprusside on the intrinsic elastic properties of pressurized rat coronary artery

Summary— The study was designed to assess the influence of either nitric oxide (NO) or sodium nitroprusside and the absence of endothelium on the intrinsic elastic properties of coronary arteries from WKY rats. For this purpose, segments of the right interventricular coronary were mounted in an arteriograph where wall thickness and internal diameter were continuously monitored while intraluminal pressure was controlled in the absence of flow. To study the passive properties, pressure-diameter relationships were determined by measuring the corresponding internal diameter for each stepwise increase in intraluminal pressure. Thus, wall stress, strain and incremental elastic modulus (E_inc) were assessed in the following experimental conditions: control, incubation with nitro-L-arginine methyl ester (L-NAME, 100 μM) or L-NAME + L-arginine (L-arg, 100 μM), incubation with sodium nitroprusside (SNP, 100 μM), endothelium removal (CHAPS). The E_inc-stress relationship was not significantly different in the different experimental conditions, but values of E_inc plotted as function of strain were significantly decreased after L-NAME incubation and partly reversed after L-arg addition. The same effect was observed after endothelium destruction but to a lesser extent. After SNP incubation, values of E_inc were significantly decreased for small values of strain and increased for high values of this parameter. These results show that NO synthase inhibition induced, for a given strain, a decrease of elastic modulus in coronary arteries. It can be speculated that functional antagonism exerted by NO against spontaneous contractile tone was reduced. Thus, the smooth muscle cells were in a greater state of activation and probably more strongly involved in the intrinsic elastic properties of this preparation. However, an unexplained effect of NO on wall stiffness cannot be excluded. Conversely, SNP increased the initial diameter and induced an initial decrease in stiffness followed by a subsequent increase. After endothelium destruction, stiffness was significantly decreased compared to control conditions. It can be concluded that NO modulates the intrinsic elastic properties of the coronary arteries through smooth muscle cell relaxation. Furthermore, results with SNP support the hypothesis that the lower the state of activation of the smooth muscle cells, the higher the elastic modulus of the arterial wall in this coronary artery preparation.