Coronary endothelium-protective effects of defibrotide in ischaemia and reperfusion

Summary Defibrotide is known to enhance prostacyclin (PGI₂) release from the vascular endothelium. We investigated the vasoactive effects of defibrotide in isolated rat hearts perfused at constant flow subjected to ischaemia and reperfusion. Defibrotide at 10^–7 or 100 g/ml did not exert any direct vasoactive effect on normal rats hearts. However, ischaemia and reperfusion resulted in an impaired vasodilation to acetylcholine, an endothelium-dependent vasodilator. In contrast, the vasodilator response to the endothelium-independent dilator, nitroglycerin, was unaffected. Defibrotide, at 10^–7 or 100 g/ml, markedly restored the vasodilation to acetylcholine 10^–7 nmol/l to 1 mol/l (P < 0.01) without influencing the vasodilator response to nitroglycerin (2 to 200 g/1). Haemoglobin (150 nmol/l) inhibited the dilation to acetylcholine in response to defibrotide. However, no evidence of (PGI₂) release was observed with acetylcholine-induced vasodilation in the presence or absence of defibrotide. Additionally, 10–100 g/ml of defibrotide did not significantly decrease superoxide radicals generated by a xanthine-xanthine oxidase synthetic system under conditions in which superoxide dismutase was effective. Thus, defibrotide appears to exert an endothelium-protective effect preserving endothelium-derived relaxing factor (EDRF) without directly scavenging free signals.Supported in part by Research Grant No. HL-25575 from the National Heart, Lung and Blood Institute of the NIH Send offprint requests to A. M. Lefer at the above address     

仁术健胃颗粒逆转胃癌前期病变的临床研究

目的观察仁术健胃颗粒对胃癌前病变的逆转作用。方法将１２０例符合诊断标准的胃癌前期病变患者,随机分为仁术健胃颗粒治疗组８０例和胃复春对照组４０例进行临床疗效观察。结果①综合疗效：治疗组总有效率为９１．２５％,对照组为７５．００％,经统计学处理,差异有显著性（Ｐ〈０．０５）;②治疗组胃镜及对萎缩、肠化、异型增生的疗效分别为７１．２５％、７７．５０％、７９．４９％、８８．４６％,对照组为５２．５０％、６     

Decreased frequency of a novel T-lymphocyte subset,CD3+CD4−CD7+CD57− T cells,in hepatitis B virus-related end-stage liver disease might contribute to disease progression

CD7 and CD57 are related to the differentiation and functional stages of CD8⁺ T cells. However, the role of their combined presence in CD8⁺ T cells in patients with chronic hepatitis B virus (HBV) infection, especially those with end-stage liver disease, remains unclear. Blood samples from healthy volunteers and patients with chronic hepatitis B were analyzed via Luminex assay and ELISA to measure plasma cytokine levels. Further, recombinant IL-22 was used to stimulate peripheral blood mononuclear cells from healthy volunteers, and the frequency of CD3⁺CD4⁻CD7⁺CD57⁻ T cells and apoptosis rates were investigated via flow cytometry. Patients with end-stage liver disease, particularly those with acute to chronic liver failure, showed decreased CD3⁺CD4⁻CD7⁺CD57⁻ T cell frequency. Furthermore, the prevalence of CD3⁺CD4⁻CD7⁺CD57⁻ T cells was negatively correlated with disease severity, prognosis, and complications (ascites). We also observed that IL-22 promoted apoptosis and brought about a decrease in the number of CD3⁺CD4⁻CD7⁺CD57⁻ T cells in a dose-dependent manner. CD3⁺CD4⁻CD7⁺CD57⁻ T cells displayed a B and T lymphocyte attenuator (BTLA)^highCD25^highCD127^high immunosuppressive phenotype and showed low interferon-γ, tumor necrosis factor-α, granzyme A, and perforin expression levels. The present findings will elucidate the pathogenesis of HBV-related end-stage liver disease and aid the identification of novel drug targets.     

Intelligence and temperament as protective factors for mental health. A cross-sectional and prospective epidemiological study

The Sjöbring system of personality dimensions measuring intellectual capacity, activity, impulsivity and sociability was used to study possible salutogenic (i.e. causes of health) effects. The study comprised 590 subjects investigated in 1947, 1957, 1972 and 1988–1989 in the Lundby project, an epidemiological study in Sweden. Psychiatric diagnoses were made in 1947, 1957 and 1972. Mental health was estimated in 1988–1989 using the concept love well, work well, play well and expect well. The Sjöbring dimensions were clinically assessed in 1972. Both in the concurrent study in 1972 and in the prospective study in 1988–1989 super capacity (high intellectual function), super validity (high activity level) and super solidity (low impulsivity) were statistically associated with lower frequencies of certain psychiatric diagnoses and a higher frequency of positive mental health. These variables are proposed to increase coping capacity, and therefore increase stress resilience.     

Effects of chronic treatment with valproate on serotonin-1A receptor binding and function

Valproate is effective in treating bipolar disorder characterized by rapid cycling or acute mania, although the mechanism of action is unclear. In contrast to other treatments for depression, 21 days of treatment in rats with valproate (100, 200 or 400 mg/kg) did not significantly alter the hypothermia induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors. Treatment with valproate also had no effect on radioligand binding to serotonin-1A, serotonin-2 or -adrenergic receptors. Based on these animal studies in frontal cortex and hippocampus, the therapeutic benefit of valproate in mood disorders does not appear to involve adaptive changes in serotonin-1A, serotonin-2 or -adrenergic receptor number.     

Effects of two stressors on behaviour in the elevated X-maze: preliminary investigation of their interaction with 8-OH-DPAT

Effects of water deprivation and restraint were compared in the rat elevated X-maze. Water deprivation for 12–48 h increased corticosterone and had a duration-dependent anxiolytic effect in the elevated X-maze, increasing the ratio of open/total arm entries (OTR) and the proportion of time spent on the open arms (% time) without affecting total entries. Brain 5HIAA/5HT was increased only after 24 or 48 h deprivation. Restraint for 15 min also increased plasma corticosterone and brain 5HIAA/5HT but had no effect on behaviour in the elevated X-maze when rats were tested immediately afterwards. However, 1 h restraint was anxiogenic in the elevated X-maze immediately after release, reducing OTR and % time, but with a less consistent reduction in total entries; reductions in OTR and % time were still present 24 h later. The 5HT_1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.1–0.2 mg/kg), administered 10 min before testing in the elevated X-maze, had anxiogenic actions in non-stressed rats. The effect of 0.1 mg/kg 8-OH-DPAT was not significantly altered by 24 or 48 h water deprivation but was abolished by restraint for 1 h immediately beforehand, despite the anxiogenic effect of restraint alone. Similar mutual antagonism of 8-OH-DPAT and restraint occurred when the dose of 8-OH-DPAT was increased to 0.2 mg/kg. Twenty-four hours after restraint, restrained rats which had received 8-OH-DPAT (0.1–0.2 mg/kg) still did not show any significant anxiogenic effect compared with non-restrained vehicle treated controls. Restraint-induced deficits in elevated X-maze exploration may prove a useful model with which to study the pharmacology of depression-related anxiety. However, the effects of the stressors examined, and their interaction with 8-OH-DPAT in the elevated X-maze, appear to depend on the nature of the stressor.     

Ear and eye representation in the frontal cortex,area 8b,of the macaque monkey: an electrophysiological study

We evoked both ear and eye movements in area 8b, the rostral area of frontal cortex, in two monkeys. In some sites it was possible to evoke only ear movements or only eye movements; in other locations we evoked both ear and eye movements by varying the intensity of electrical stimulation. The electrically evoked ear movements were forward, or backward, or oblique (upward-forward; upward-backward). In two penetrations the ear movements were bilateral, in the other penetrations they were contralateral. Ipsilateral ear movements were not observed. The evoked eye movements were mainly fixed-vector saccades, contralateral and with an upward orientation of about 45°. If we considered only the sites where the threshold was equal to or lower than 50 A, the stimulation of this area evoked mainly ear movements. In addition we recorded the electrical activity of 195 neurons. Of these neurons: 74% (145/195) discharged before ear movements (ear cells); 20% (40/195) discharged before ear and eye movements (ear-eye cells); 5% (10/195) discharged only before eye movements (eye cells). Ninety-one percent (132/145) of ear cells presented a preferred direction; 90% (36/40) of ear-eye cells presented a preferred direction for ear movements, and 15% (6/40) presented a preferred direction for eye movements. Eighty-five percent (34/40) of cells did not present a preferred direction for visually guided saccades and were active when the monkey made saccades toward the unlit targets (checking saccades). Our results show that a field of area 8b is related to ear movements and to eye-ear movements. The findings that it is possible to obtain both ear and eye movements with low-intensity currents and that there are cells firing for the two types of movements suggest that area 8b may be involved in the orientation and coordination of both ear and eye. This area might be considered a rostral extension of supplementary eye field (SEF) or a different region. However, based on its distinct functional characteristics and connectivity, it is probably better regarded as a separate field. Regardless, the combination of 8b and SEF may constitute a cortical center for orienting processes.     

Pediatric intestinal transplantation

Advancements in donor management, organ preservation and operative techniques, as well as immunosuppressive therapies, have provided children with intestinal failure and its complications a chance not only for enteral autonomy but also long-term survival through intestinal transplantation (ITx). First described in the 1960’s, experience has grown in managing these complex patients both pre- and post-transplant. The goals of this review are to provide a brief history of intestinal transplantation and intestinal rehabilitation in pediatric patients, followed by focused discussions of the indications for ITx, induction and maintenance immunosuppression therapies, common post-operative complications, and outcomes/quality of life post-transplant.     

骶后孔解剖学测量及临床意义

目的：通过对骶后孔位置的研究,进一步解决在针炙临床中对八穴定位不准的问题。方法：用游标卡尺对骶后孔的纵、横径及骶后孔间径进行测量,并作统计学处理。结果：测算出100例骶骨（男性54例,女性46例）骶后孔纵、横径和骶后孔中心距后正中线间横径及骶后孔中心间纵径的数值。并结合这些数值,提出比较准确的八穴的定位方法。结论：骶后孔中心距后正中线间横径及骶后孔中心间纵径对八穴的准确定位具有重要指导作用。此外,骶尾椎和腰椎骶化变异对八穴取穴也有一定影响。     

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.