弯曲血管内血流与动脉粥样硬化斑块的相互影响与作用

作为文章[1]的继续,本文在文章[1]的分析结果基础上,针对壁面对称和非对称狭窄的两种不同情况,通过数值计算给出弯曲狭窄血管内血流的轴向和周向切应力的分布曲线,并讨论其随管壁面几何参数的变化情况。同时,还讨论壁面几何参数对平均血流量和压力降影响的规律。从中发现,当狭窄较轻时(λ<0.2),壁面切应力、平均流量和压力降受狭窄度(λ)的影响不大,而在狭窄较严重时(λ>0.7),狭窄度微小的变化会引起它们急剧变化。此外,在讨论狭窄的非对称性对上述血流动力学参数的影响时还发现,非对称性只对轴向切应力有明显的影响,而对其它参量的影响并不十分显著。     

Psychological functioning across stages of treatment for infertility

Psychological functioning was examined for a cross section of 104 couples in different stages of medical investigation for infertility. Couples were separated into three stages based upon the length of time they had been pursuing medical treatment for infertility: year 1, year 2, and year 3 and beyond. Emotional strain was moderately elevated during the first year, returned to more normal levels during the second year, and showed marked increases beyond year 3. Indices of marital adjustment and sexual satisfaction were stable across the first two stages but deteriorated after the third year. These data suggest that the stage of treatment may exert a major influence upon psychological functioning for infertile couples pursuing medical assistance. The results are consistent with a model of psychological strain that reflects an acute stress reaction to the initial diagnosis and treatment overlaid with a chronic strain response to longer-term treatment.Research was aided by a grant-in-aid of research from Sigma Xi, The Scientific Research Society, a research fellowship from the University of South Carolina, and NIMH Institutional Training Grant MH-15930.     

Exercise improves biomarkers of health and stress in animals fed ad libitum

Voluntary and forced exercise decrease morbidity and mortality in laboratory animals. Caloric restriction has similar effects on health and unique benefits on life span. Nonetheless, in most experiments, animals do not have access to physical activity and are fed ad libitum (AL). We hypothesized that with regular access to either unlimited running wheel exercise (EX) or limited physical activity (PA), key biomarkers of health would be enhanced enough to counter some consequences of a sedentary AL lifestyle. This 16-month study compared body weight, tumor number and size, tissue lesions, oxidative stress, and reactive stress in (1) sedentary animals with no access to physical activity (SED); (2) animals with access to hour-long, twice weekly activity in a large box (PA); and (3) animals with access every other day to a running wheel (EX). At the end of the study, EX body weight was 8-9% lower than PA and SED. In addition, EX had no kidney lesions versus 50% in PA and SED, and had smaller tumor size (10+/-2 vs. 14+/-4 and 30+/-4 mm). Exhaustive exercise lowered glutathione/oxidized glutathione ratio in EX and PA, but in SED, the ratio was depressed even in resting animals. In all treatments, prolactin (PRL) levels were lower in resting animals than in acutely exercised animals. In conclusion, EX had the most favorable health biomarkers while SED had the least. PA did not confer gross health benefits different than the SED group, but was biochemically more similar to EX animals.     

Electromyographic and affective responses of episodic tension-type headache patients and headache-free controls during stressful task performance

Thirty-four subjects meeting diagnostic criteria for episodic tension-type headache and 42 who rarely experienced headaches participated in two laboratory sessions in which cephalic electromyographic (EMG) activity, electrodermal activity, heart rate, and finger temperature were recorded. Subjects performed relaxation, choice reaction time, psychomotor tracking, voluntary muscle contraction, and cold pressor tasks. Headache subjects showed significantly greater EMG activity than controls during baseline and stressful task performance. During relaxation, both groups reduced EMG activity from baseline levels, and there was no significant difference in EMG level between the groups during relaxation. Headache subjects reported higher levels of subjective anxiety, depression, anger, and stress than controls. Headache subjects also reported higher levels of pain than controls, and headache subjects reported greater pain during stressful task performance relative to baseline and recovery periods.This research was supported by NIH Grant R01-NS-25114.     

High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety

In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.     

Endothelial Regulation of Vascular Repair: Role of bFGF in Paracrine Pathways

Vascular repair following injury is mediated by both endothelial and smooth muscle cells often through paracrine pathways. Basic fibroblast growth factor (bFGF) is present at sites of vascular injury. The role of bFGF in regulating reendothelialization through an effect on centrosome redistribution in cell migration is discussed. The role of bFGF in neointimal formation, especially as it relates to smooth muscle cell proliferation, is reviewed. It is concluded that bFGF appears to be an important agent regulating the early responses of the artery wall to injury. Presented in part at the Molecular Endocrine Pathology Symposium at the International Academy of Pathology XXI International Congress, Budapest, Hungary, October 20–25, 1996.     

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

Spontaneous and oxidative stress-induced programmed cell death in lymphocytes from patients with ataxia telangiectasia (AT)

T cell lymphopenia in the peripheral blood lymphocytes (PBL) of patients with AT is mainly caused by a decrease of naive CD45RA+/CD4+ cells followed by a predominance of memory CD45RO+ lymphocytes. To relate these findings to the regulation of programmed cell death, we investigated the activation state and apoptotic level of PBL in 12 patients and healthy controls by flow cytometry. In accordance with previous investigations, the number of naive CD4+/CD45RA+ cells was significantly decreased in patients compared with healthy controls. This disturbed balance of CD45RA and CD45RO was also reflected in higher amounts of activated HLA-DR and CD95 expressing cells, with a concomitant decrease of Bcl-2 protected lymphocytes in the T cell population. With regard to its role in preventing oxidative-induced cell death, we analysed Bcl-2 expression and apoptosis in the presence of oxidative stress. In culture, cells of patients are more susceptible to spontaneous programmed cell death. However, in our stress-inducing system (hypoxanthine/xanthine oxidase system) the number of cells undergoing apoptosis was lower in patients' cell populations compared with controls. In addition, preliminary results suggest that Bcl-2 expression and level of spontaneous apoptosis in patients can be modified by IL-2 and interferon-gamma.     

Thermal pleasantness sensation: an indicator of thermal stress

Summary The degree of pleasantness or unpleasantness of thermal sensation aroused by a particular peripheral thermal stimulus has been shown to be an indicator of thermal state of the body in relation to the thermoregulatory set point. This phenomenon is known as thermal alliesthesia. The quantification of thermal alliesthesia was possible using two methods: (1) A set of temperature stimuli (15, 20, 25, 30, 35, and 38 C) was applied, by means of a Peltier thermode 5.5×2.7 cm², on the back of the hand, the forehead, and the back of the neck. When each stimulus had been applied for 5 s the subjects voted their degree of thermal pleasantness/unpleasantness on a psychophysical scale ranging from +2.0 for very pleasant to –2.0 for very unpleasant. (2) The subjects were also asked to adjust the Peltier thermode temperature, without looking at the temperature scale, such that the temperature (on the back of the neck) was maintained at the level the subjects considered most pleasant. The subjects also rated their general thermal comfort sensation on a five point scale ranging from +2.0 for very comfortable to –2.0 for very uncomfortable. Rectal temperature and skin temperature at eight locations were continuously recorded. Passive thermal exposures (54) were made with nine passive subjects and 42 exposures were done with working (50 watt) subjects. All exposures were carried out in a climatic chamber at a constant temperature, relative humidity (45%), and air speed (0.3 m/s). Each subject underwent 6 exposures at six room temperatures of 15, 20, 25, 30, 35, and 40 C. The results of work exposures confirmed the findings of previous studies; namely, the effect of core temperature change overrides any effect due to mean skin temperature on alliesthesial response. A mathematical function to predict the mean slope of the thermal pleasantness rating/stimulus line (a measure of the alliesthesial response) was derived using the data obtained from the passive thermal exposures. The results indicate that alliesthesial response can be used as a quantitative indicator of thermal stress.Supported by the European Coal and Steel Community, Luxembourg     

Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease

Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two-step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H(2)O(2)), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non-inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up-regulation of Mn-SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM-mediated damage, these changes should be coordinately counterbalanced by an increased H(2)O(2)-neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and/or localization of the most prominent mucosal H(2)O(2)-related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H(2)O(2)-metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H(2)O(2)-mediated damage seemed to be restrained by the increasing numbers of CAT- and MPO-positive monocytes/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro-inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH(*)) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H(2)O(2) is hampered in these cells, thereby increasing not only the risk of detrimental effects of H(2)O(2) directly, but also those of its extremely reactive derivatives such as OH(*). Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes.